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U. S. DEPMTMENT OF HEALTH, EDUCATION, AND WELFARE
PUBLIC IffiALTH SERVICE
OPERATING EXF'ENSES . NATIONAL INSTITUTES OF HEALTH
(statement of Dr. Uilliara H, Sebrell, Jr., Director of the National Institutes
of Health, before the Labor-Health, Education, and Welfare Subcommittee of
the Committee on Appropriations)
Post"War Medical Research in the U.S«
As a Nation, we are nov/ in the fifth year of an expanded medical
research effort. During that period there has been a most remarkable grov/th
of both private and public support for medical research and for training
medical research manpomer.
This upsurge of support is concrete evidence that the American people
have firmly endorsed both the humanitarian and the direct economic gains to
be achieved ultimately by medical research* ITe have, as a Nation, adopted
by the force of logic and public opinion two policies:
Capable investigators should be supplied nith the funds they need to
exploit their ideas fully.
Additional manpo?/er of high caliber should be trained to expand our
National research capacity*
In the evolution of these tno lines of policy, the Congress has been
a leader, both through establishing the structure for research in the form
of National medical research institutes and through providing substantial
appropriations to make the machinery operative not only in these institutes
but also in non-governmental research and teaching institutions.
In the light of these developments, vie need not take time to reiterate
the significance of the disease problems in economic terms and in terms of
suffering among individuals and their families, ..
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The time has come when it is no longer valid merely to complain of the
problems created by chronic disease; we should be able to point to concrete
advances achieved over a wide front. The concentration of brains and
facilities over this period leads to a legitimate expectation of solid
These advances are being made, and at every level, from fundamental
laboratory work to direct clinical application.
The Institute Directors will indicate in some detail the recent
accomplishments of investigators throughout the Nation in their respective
fields of categorical responsibility, but a brief check list here will indi-
cate a tremendous vitality and forward surge in a wide array of fields.
In the field of mental diseases, there are firm leads that begin to
explain some mental disorders in terms of biochemical differences between
the normal and the mentally ill person. This is a general development of
the utmost significance. At the same time, advances on the psychiatric and
psychological fronts are opening the way to more precise early identification
of those who will and those who will not respond to established treatment
procedures. The development of reliable tests in this field will effectively
multiply the efficiency of our limited manpower and treatment facilities.
In heart disease, the discovery of new anti-clotting substances has
resulted in the saving or prolonging of many lives. Drugs have been
developed which can stop often fatal arrhythmia-irregular heart beats —
and a more precise understanding of cardiac failia-e has permitted the
development of more rational treatment. This latter advance has not only
increased the life span of countless cardiacs but has returned vast
numbers to comfortable and profitable employment.
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In the neurological field, significant progress against epilepsy as
a significant disease is presaged by the first fruits of research - the
discovery of new drugs, advances in surgery, and a beginning understanding
of basic biochemical defects which characterize this condition. The sacred
scientific trviism that severed nerves in the central nervous system cannot
grow back together has been disproved, a discovery that opens a whole new
field of study of great potential practical importance.
In the cancer field, a positive, simple test for cervical cancer has
been found. Of particular importance in this regard is the developing con-
viction, based on sound observations, that a detectable pre-invasive condition
is the rule rather than the exception. The disappearance of this form of
cancer as a serious heialth threat now depends solely on early detection and
treatment. Radioactive isotopes are providing both better diagnostic
techniques and better treatment for certain other forms of cancer.
In the field of arthritis, rheumatism and other metabolic diseases,
use of ACTH and cortisone as treatments has been widely publicized, as have
some of their deficiencies. Equally stimulating to medical scientists is
the avenue of study that these and related chemicals have opened up—
studies directed towards an understanding of the underlying causes of the
wide array of these related diseases.
In the field of microbiology, recent advances have centered attention
on viruses and bacteria as the cause of some chronic and degenerative diseases
as well as acute infections. This is quite a new approach to the significance
of microbiological agents, and one of tremendous potential significance.
In short, the first big National push in medical research is beginning
to pay off even within a five-year time span. And five years is a short
period in medical research. It can be confidently predicted that the flow of
productive findings will grow if medical research is supported amply and
It can also be predicted that many answers ^^^ill not be found for
decades. This is not a cause for despair, for experience has already amply
shown that very real progress in saving lives can be made before ultimate causes
In reviei-iing the general status of irBdical research and the recent ad-
vances, one of the developments that emerges most clearly is the rapid ex-
tension of productive biochemical and biophysical studies into the medical and
biological fields. Medical research is coming of age as a quantitative science.
There is perhaps no more fundamental trend in medical research, and no trend
which it is more important to encourage.
This development must be nurtured by funds, for equipment and
competencies from the physical sciences which are essential to these studies are
e:q)ensive. It must be nurtured by patience, for the studies are almost
infinitely complex. It must be nurtured by proper organization for reseairch,
because the final fruition of medically related research in the physical
sciences is through a productive partnership with clinical research.
Against this background of general National developments in medical
research, we can assess developments in the .programs of the National Institutes
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MAJOR PROGRAii DEVELOPI'fcNTS AT THE
NATIONAL IMSTITUILS OF HEALTH, F.Y. 195U
Development of Gap Areas — Neurology and Blindness j and Arthritis
In establishing National medical research Institutes, Congress assumed
that by setting up an organization and providing funds, research in lagging
areas could be stimulated.
It is gratifying to report that this assumption has proved to be sound
in the fields of Neurology and Blindness, and Arthritis and Metabolic Diseases,
A major program development has been the rapid maturing of the NeuroloQr
and Blindness Institute to achieve a dimension which begins to approach the
importance of the problem. You will recall that this Institute was established
in 1950 and received its first appropriation in 195l« Today, it has gathered
together a brilliant young staff and is already conducting and supporting
significant studies in epilepsy, multiple sclerosis, cerebral palsy, and the
other neurological and sensory disorders. The initiative and drive of this
group has been one of the high points of the year.
At the same time, as Dr, Bailey will report in detail, the entire field
of neurological research throughout the Nation has been encouraged and
And all of this has gone forward not tlirough Federal direction or control
of individuals, institutions or organizations, but through a close collaborative
A comparable development has taken place in the Arthritis Institute,
In spite of the enormous importance of the rheumatic diseases (there are now
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about 10 million victims of arthritis and rheumatism in this country), the
public and to a degree the professional world was apathetic about these
diseases. Then, in quick succession, there came a series of events which
reversed the trends, The Arthritis and Rheumatism Foundation was established
to raise funds and lead the way in professional and public education. The
National Research Council set up a National scientific committee to assess
progress, problems and gaps in the field, Ihen there was the dramatic
annoiincement of the discovery of cortisone and ACTH» Finally, under the
Omnibus ifedical Research Act in 1950 - the National Institute of Arthritis
and Metabolic Diseases was established. In this last three years, using
revolutionary research approaches and strengthened by strong private and
public cooperation, it has become eviaent that this field, like neurology,
has come into its own. Just several months ago there was held at Bethesda
the first Ifetional symposium ever to be held on research and research training
in the arthritis and rheumatism field.
Initial Operations in the Clinical Center
One of the major program developments at the National Institutes of
Health, as you gentlemen have good reason to know, has been the opening and
initial occupancy of the Clinical Center. I will not attempt here to
recapitulate what this facility has meant to our research program by making
it possible for us to integrate laboratory and clinical investigations.
Suffice it to say that the mere existence of this structure on our campus has
had implications that reach to the very roots of our scientific programs.
As might be anticipated, we have had to pay a great deal of attention
during the past fiscal year to the sheer mechanics of moving into the Clinical
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Center. We have been concerned with such things as the timing of purchasing
supplies and equipment, planning space occupancy to encourage integrated
research effort, establishing the policies governing care of patients and their
relationships with the research environment, adjusting laboratory design to
meet the specialized needs of investigators who were not employed when the
initial plans were made, and re-planning occupancy, purchasing, and staffing
schedules when contractors have failed to meet specifications or deadlines.
These may appear to be matters of detail, but we have found that the
satisfactory resolution of a vast array of details is in practice the only
way we can progress towards ovir general objectives.
The entire staff has worked hard and has been most cooperative in
bearing with the inevitable delays and frustrations that are involved in such
a complicated undertaking. In the face of these problems, patients have been
brought into the Center, the medical care provided them has been excellent,
and clinical research has begun in all Institutes.
One of the most important elements of our work related to the Clinical
Center has been the establishment of good working relations with physicians in
private practice, professional groups, and medical institutions. The good
will and support of these groups is important in the referral of patients,
in the use of consultants, and —most important— in the ability to establish
and maintain the many kinds of formal and informal cooperative working
relationships which are the heart of any successful medical undertaking.
There are more than a hundred study patients in the Clinical Center
today. We anticipate that there may be over 200 by July 1. There is
virtually no way in which this research facility resembles a general
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hospital (in which the patient day costs can be accurately predicated) save
in the quality of medical care we provide. There the similarity ends. The
research design may demand specieil diet, frequent tests, extra nurses,
expensive medicinals, total isolation — all factors which might be
essential to research but serve to render valueless any presimptive base-
line data seeking a standard by which to convert dollars into patients.
It might not be amiss for me to reiterate that in the Clinical Center, the
welfare of the patient comes first. It is to my best interest and that of
the scientific staff to fill the Clinical Center beds with patients and
keep them filled, to the limit of our program needs and the resources
available to us. But without experience data, I cannot and will not
stretch the limits of good medical care and disrupt the standards of
good research practice in order to meet a ratio of dollars to beds.
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RESEARCH GRANTS . RESEARC H TRATNTOO, ftAi p pTS^ASE CONTROL
I. Research Grants
The basic, tested policies underlying the research grant programs
have remained basically unaltered.
We plan to continue support, not only to clinical investigations
and research directly applicable to medicine, but also to studies which
are relevant to underlying problems but not immediately applicable to
medicine. We consider this approach to be so important that - in addition
to giving it support from the programs of the various Institutes - we have
a program under the Division of Research Grants directed especially to
support of basic studies which have a direct relationship to medicine
as a whole instead of to single disease categories.
We initiate large- scale coordinated research programs when there
is a firm scientific consensus that this approach is profitable.
We continue to rely heavily upon the judgment of university and
other non-Federal scientists in assessing the worth of proposed projects,
and particularly the caliber of men. We continue to seek general policy
advice from National Advisory Councils.
The esteem in which the program is held in the scientific and
academic worlds continues to be a source of satisfaction to us, as it
must be to those Committees of Congress which have sponsored our enabling
legislation and assumed our continuing support of research and research
training by establishing our level of expenditure.
This is not to say that we do not face problems. We have some
very real ones. For example, we are continually assessing the extent to
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which the year-to-year project grants provide the kind of long-term
stability needed for research. We have worked out means of providing
reasonable stability, and are constamtly considering modifications to
make the programs more satisfactory.
As another example, we have been seriously considering whether we
are compensating institutions adequately for the costs that they incur
when we give their staffs research support. This is the perplexing
"indirect cost" problem that has been with us since the program began.
We are proposing a policy change during the coming year that will be
discussed when we outline the prospects for fiscal year 1955.
I I . Man ppwer Training — Fellowships, Teaching Grants, and Traini ng Gran t^
In common with all scientific fields, medical research faces the
prospect of shortages in the future unless training now is accelerated.
Two considerations are particularly significant in the manpower
picture in medicine. First, the advance of medical research has been
80 rapid that specific training is reqxiired to bring the findings to
the point of application. Second, there is an extreme shortage of
people in specific fields — of which mental health is perhaps the
In combination, the fellowship, teaching grant and training
grant programs are designed to meet these problems. The Institute
Directors will indicate the specific manpower problems faced in their
areas of interest, and the manner in which the manpower programs are
tailored to meet the needs of specific fields.
III. Control Grants
It is becoming increasingly clear that much chronic disease
which will strike millions of people can be dealt with effectively
if the existence of the disease can be found early enough. EvBn without
a full knowledge of cause, we now know more about how to halt the
progress of meiny chronic diseases than is being fully applied.
The control grants are our effort to close the gap between
scientific knowledge and application of findings to patients.
In this area, too, the Institute Directors will tell you
specifically what the control measiores are accomplishing.
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PROGRAM DEVELOPMENTS AT N.I«H. - FISCAL YEAR 19gg
THE 1955 BUDGET PROPOSALIK BROAD OUTLIl^
While the National Institutes of Health budget is complicated in detail,
the essentials of program policy underlying the figures are simple.
The 1955 budget proposes that the total research grants, research train-
ing, and disease control areas be financed at a somewhat lower level than in
195U — $l|6»3 million as compared with ^5^8,6 million.
In the direct operations of the National Institutes of Health, the 1955
budget is at the 1951^ level, except for increases required primarily for the
increased patient load and other research facilities in the Clinical Center
contemplated in 1955i
These generalizations do not apply uniformly among all the Institutes;
the differences will be covered when the Directors explain the essentials of
their 1955 budgets.
The Year Ahead at the N,I,H. Laboratories
■'■ • The Unique Opportunity and the Unique Problems
The coming fiscal year is a critical one in the development of the
National Institutes of Health, We are attempting to work out a new approach to
medical research— integration of laboratory research with research on patients
on a scale never before attempted. Never before in the history of medicine has
it been possible to bring together in one place the full array of diverse talent
that modern medical research requires.
We owe an incalculable debt to Congress not only for making available the
funds required for this pioneering enterprise, but also for establishing the
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medical research Institutes that give us a series of well-rounded frameworks on
which to build our programs.
Our responsibility, which we feel most keenly, is to make the most of
the unique opportunity that has been given to us. Our central objective is
to set the general policies that i^rill result in the greatest volume of re-
search of the highest caliber that can be extracted from the funds made avail-
able to us. This means that we have the strongest interest in economy and
efficiency so that the research dollar will be most productive,
The task of creating an institution where research can be truly integrated
and productive is extremely complex and difficult. Many of the problems are
intangible, but nevertheless of central importance,
A, Staff of Tcp Caliber
Obtaining men of the highest quality is fundamental. Given a salary
scale that is far below what industry can pay and particularly below the amounts
that qualified clinicians can earn, we have done very well in attracting
excellent scientists. In the two or three years ahead, we shall continue to
fill in other key positions. Our recruitment is spread over about a six-year
period not only because of the care we take in selecting people, but because
we wish our hiring to cause the minimum disturbance to medical schools,
hospitals and universities,
B, Ensuring Collaboration
Another matter of concern to us is to create the general expectation
that collaborative work among Institutes and between clinicians and laboratory
people is the normal way of life. Here we are working against fairly
prevalent attitudes. The physician often feels that the scientist has no
understanding of patient care and hence a subordinate role in clinical studies.
The scientist in turn often believes that the physician has no appreciation of
the ej^erimental method and hence is not a fully competent scientific colleague.
We have to modify these attitudes to build the kinds of research teams we are
At the same time, we have to make sure that the individual who fvuictions
best and has a great deal to contribute as an independent individual is given
an adequate chance to produce,
C, Hal nt aining ComTHTunic ati on
In viewing the evolution of the National Institutes of Health towards
our ideal, we see the maintenance of scientific communication— the easy exchange
of ideas and facts— as critically important, Wfien people are expected to work
with others xirhose fields ax^e relatively strange to them, there has to be a
common meeting ground of understanding. Even within one scientific field,
knowledge and ideas increase so rapidly that a scientist is hard put to it to
keep up with his field. And if he does not keep up irdth his field, he begins
to ■ a second-rater, lie feel almost a moral obligation to those who have chosen
to throw their scientific careers in with us to provide the chance for growth.
This is not a matter of personal satisfaction for scientists either, but a
matter of setting the conditions which enable them to do their jobs well.
An indispensable element of scientific communication is the ability to
meet scientific colleagues. One of the differences between an in-bred, sterile
research organization and one that is vigorous and productive is the range of
contacts of the staff, !je feel that investment of a moderate part of our
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appropriation in travel to scientific meetings pays for itself many times over.
For the coming fiscal year, it is important that we have funds to allot to
travel to scientific meetings in sufficient amounts so as to provide real
implementation to the acquisition of the vital new views and information that
are such an important stimulus to high quality research.
D, Institute— Clinical Center Integ ration and Flexibility
Another problem on which we continue to work is the integration of
seven separate Institutes in a single building. This involves a delicate
compromise between centralization of services that can be most economically
and most effectively performed by a single Clinical Center organization, and
retention in the Institutes of decisions-particularly on the research side-
that must be left to the individual programs. This is an internal management
problem that we are settling ourselves.
In integrating research, flexibility-the ability to shift men and
resources as the needs of specific investigations may indicate--is of key
importance. Any impediment to our ability to push our resources quickly and
easily into the areas of research where a stronger effort is needed will reduce
the research return on the investment in N.I.H. It would, for example, be most
difficult for us to conduct studies most effectively if our budget were
arbitrarily divided into "clinical" and "laboratory" components and this
compartmentalization were carried over into program operation. There is a
good deal of work that is purely clinical or purely laboratory, but there is
also the vital area-at the heart of the concept of the Clinical Center-where
freedom to move in either direction is essential. We are most appreciative
that the Congressional budget gives us this degree of freedom, and we intend to
show by results that the action is wise.
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In terms of general development of the research program at N.I.H., the
budget provides for the activation of 350 beds by the end of fiscal year 19^$*
We believe tlrnt the clinical care funds and the research funds to be so
balanced in the budget that we can both take good care of this number of
patients and build a sound research program around them. Of course, the
welfare of the patients comes first, and we xjill always keep the number of
patients within our capacity to provide the best medical care,
II* Evolution of Clinical Research
As the number of patients increases, each Institute will move pro-
gressively to include a type of research where groups of patients with similar
diagnoses and other characteristics are the basis for clinical studies. To
date, a substantial portion of the clinical research has had to be on a series
of individual patients. The group approach will not only speed investigations,
but make them more effective.
At the same time, specific clinical studies will become more detailed,
complex and refined. During the current fiscal year, the depth of most studies
was limited by operating problems associated vjith inaugurating patient care and
by 'he fact that some key investigators had not yet been recruited,
III, Prospective D evelopme nts in the Grant Program s
A, Research Grants
The medical research talent and facilities of the Nation are not yet
receiving support at the optimum level from the scientific vievrpoint. The
budget proposal for 1955 in the research grants field—a total of i?27,7 million-
is not a proposal that will move the Nation forward to^^rard attainment of the
optimum level. In this period of fiscal strain, the general economic effects
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of Federal expenditures as well as research considerations must of course be
taken into account in setting medical research grant levels,
VJe all look forward to the day when heavy domestic and foreign defense
ejcpenditures can diminish so that a greater share of the product of our
economy can be devoted to health and other areas of productive effort. Mean-
while, we can improve the program by paying careful attention to the way we
handle the funds.
Beginning in fiscal year 19$Sf we hope to make an administrative
adjustment of minor importance in total budgetary terms, but of substantial
iirportance to scientists and the institutions with which they are affiliated.
This change is an increase from a maximxim of 8 percent to a maximum of 15 percent
in the proportion of a research grant which will be allovjed for the indirect cost
of research undertaken by grantees. It has become increasingly clear that the
lower allowance now in effect falls far short of meeting the costs which schools
must meet when one of their staff members receives a grant from us. The school
has to provide utilities for the laboratory, expensive library service, housei*i
keeping services, and so forth, that are not part of the direct costs of research.
We believe that by increasing this allowance to 1^ percent, we will be dealing
more equitably with the institutions. Even the increase to a maximum of 1$
percent will not fully cover all of the indirect costs in many institutions.
But we continue to believe that a sharing of the costs of research, rather than
a 100 percent Federal assumption of costs, is a sound policy,
A new program in the field of chemotherapy of cancer will come into full
flower during fiscal year 19^5. This new venture, initiated during the coming
year, is a highly organized multiphasic approach, the primary target being the
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lymphomas, more particularly leukemia. The program wi3-l bring the biologist,
the organic chemist, the pharmacologist and the clinician together in an
integrated program. Its progress will be guided by group direction within
a framework that permits such rapid interchange of information as is usually
not possible outside of a single organizational unit. The program was
initiated in the belief that exploration of this particular field, in the
particular manner and at this particular time will be highly rewarding....
perhaps as great as was the case in other fields of chemotherapy such as
the malarias and bacterial diseases.
B • Teaching and Training Grants
In the manpower area — teaching grants, training grants, training
stipends and research fellowships — the functions and objectives of the
programs remain as they were in earlier years. The level of the programs
will be reduced in 1955 about 10 percent below the 1954- level. As in the
case of research grants, this represents not a reduction in need, but an
adjustment to the realities of the Federal budget.
We anticipate further strengthening of medical school curricula in the
heart and cancer fields if the budget is adopted.
We also can predict that about 90 percent of the research fellows will
continue to remain in the medical research field.
C . Grants to States for Control of Digease
As the flow of research findings is augmented, the productivity of
measures to control chronic disease in the States will increase.
The grants to States administered by the Mental Health, Cancer and
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Heart Institutes, proposed at the sv5»7 million level appropriated in 19Shf will
complement efforts in other fields that are administered by the Bureau of State
Services, The Institute Directors are prepared to explain the variety of early
detection and diagnosis techniques applicable to the specific disease groups,
We are pleased to be able to report accelerating progress in virtually all
fields of medical research.
This progress has come about not by chance, but as the result of joint
pub lie -private support of medical scientists. This support has come at a time
when a solid scientific justification for intensified effort is warranted. The
support has been provided from both public and private sources in a way that has
expanded rather than limited the ability of scientists to do what they consider
most productive. Those of us whose life work is medical research, are truly
appreciative of the understanding and support iirhich has always marked both the
deliberations and the actions of this Committee,
The Nation is now reaping dividends on its investment. With reasonable
stability in support and ^^risdom in handling funds, we can look forward to
continued progress < '
Ernest Me Allen
Chi.ef , Division of Research Grants
National Institutes of Health
Public Health Service
COMITTEE ON APPROFRIATIONS
"Operating Expenses^) National Institutes of Health (Division of Research Grants)"
tlr. Chairman, and members of the Commttees
The Division of Research Grants, National Institutes of
Health, was established by the Surgeon General of the Public
Health Service in 19U6 under Congressional authority included
in the Public Health Service Act of 19hho The Division has two
functions? one, to provide teclmical review and certain admini-
strative services for all Public Health Service research grants
and research felloiirahips; the other, to administer the general
research grants program (identified in the Appropriations Bill
as Operating Expenses, National Institutes of Health),
Miile many major areas of medical and biological research are supported
by the seven Institutes of the National Institutes of Health, highly important
segments of the total research needs raiist still be supported from the general
research grant funds. Although this program is not oriented towards groups of
specific diseases, the research it supports will give rise to new knowledge
which may well serve as the baseline for significant research acconrplishments
in any one of the many categorical areas of research*
Support for fundamental and clinical research not provided by the
Institutes must be maintained and, as conditions and funds permit, expanded
as a most effective means of asstiring advances in the total field of health.
For 19$6 it is proposed to continue this program and to expand two programs
of research that urgently demand special attention and emphasis. The first
of these, water pollution, will require an additional |1, 000, 000 for research
grants; the second, research on improved nvirse utilization, an additional
COWTBIUATIOM OF CURRENT ffiOGRM
The special mission of the noncategorical program is to bring fimda-
mental medical research to the point where application to a specific problem
can be seen. Support for this type of research requires soroeiArhat more than
half of the available funds ;, yet its importance is not readily understood.
Even the highly- trained scientists who make such studies almost never
appyeciate at the outset what the practical benefits may be. Nevertheless ^
progress in clinical medicine would soon cease if fundamental research were
Oftentimes the proposed fundamental research is recognized by an
Institute as most appropriate for support. In many instances ^ however, the
work is of such nature that it does not appear to be pertinent to the
objectives of the Institute, or the proposed investigation may have such
broad application that no single Institute has the particular interest
needed to ensure support. Meritorious projects of this character will be
supported from general research grant funds. A good example of the latter
type is a grant recently made to a young professor of chemistry, considered
a genius by many of his fellow scientists. This grant was paid from general
research grant funds because his studies covered a variety of natiu'al products,
including synthesis of quinine. On December 26, 195Uj the New York Times
announced that this investigator had successfully synthesized strychnine and
used this fact as the first of several reasons for concluding that 195U had
been a "stimulating year in chemistry."
The importance of fundamental research is best demonstrated after the
practical applications are known. The value of arainopterin in prolonging
the lives of children stiff ering from acute leukemia is well known to this
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Committee, which has shoivn great interest in cancer chemotherapy. Historically,
though, aminopterin grevf out of studios of the yellow pigment of butterfly
■vvings and studies of the effect of sulfonamide drugs on the bacteria v/hich
grow in the intestines of rats. Another recent medical milestone, also v;ell
knovm, is the discovery that ACTH (adrenocorticotropic honnone) and cortisone
remedy conditions which had previously resisted all kno\vn forms of treatnent,
I know this Committee will be pleased to recall that prior to this discovery,
a grant of $30,000 from the Division of Research Grants' funds stimulated
the production of ACTH in sufficient amounts to keep research in this area
alive. This early work, unrelated to any specific disease, laid indispensable
ground work for the dramatic clinical findings v/hich came later.
This program has continued to support fundamental studies of the
pituitary hormones and only recently tvio nev; brealc-throughs have occurred.
Scientists at the University of California have succeeded in isolating
extremely concentrated preparations of growth hormone which in early tests
have greatly increased the efficacy of ACTH in the treatment of malignancies.
A quite different milestone was passed at Cornell University where a grantee
succeeded in synthesizing another pituitary hormone, oxytocin, which for
years has been widely used to aid childbirth and lactation. This is the
first occasion in which man has manufactured in the test tube a biologically
active protein-like substance. Knowledge of the chemical components of this
substance vdll aid in fvirther study of the use and limitations of ojcytocin.
More importantly, this discovery of a m.ethod for taking the amino acid
building blocks and constructing a functional fragment of a protein brings
us a stop nearer to the understanding of life. Itself and paves the way for
future advances in the test tube synthesis of proteins Virhich heretofore could
be manufactured only in the living body.
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In addition to these fundamental studies, the general research grants
program of the Division of Research Grants supports a wide variety of research
on clinical probleius, such as those represented by the follov:ing areas.
Fetal and neon atal deaths . Over the past 50 years, scientific advances
have resulted in a rpectacular reduction of infant mortality. The infant
death rate has dropped from l62 per thousand in 1900 to 31.8 per thousand
in 1950j but this means that over one hundred thousand babies still die each
year. Furtherrrore, conservative estimates of stillborn children would run
into the hundreds of thousands yearly.
The causes and methods of prevention of some of these deaths are
already known so that some improvement can be expected by wider application
of existing knowledge. To a great extent tho causes in the majority of
cases remain unknovm and methods of prevention must await further research.
The general research grants program is supporting some v/ork in this area.
For example, a cooperative study by investigators in different cities on
the causes of sudden death of infants in apparently good health has uncovered
the surprising fact that an intensely severe i-espiratory disease was often
present in infants presumed to have died of mechanical suffocation. This
research has not only posed a new research problem, but also contributed
to the alleviation of the mental anguish of parents who might blame them-
selves under the tragic circumstances.
Diseases of the gastrointestinal tract . For the average family, the
great burden of medical expense and the great toll of human suffering are
tho result of diseases vrhich are not fatal. Many of these fall v/ithin the
area of responsibility of the general research grants program. For examrale,
diseases of the gastrointestinal tract are of coiviaon occurrence. It has
been estimated by experts that one of these diseases, peptic ulcer, afflicts
12 percent of all American adults at one time or another. In World War II,
the Armed Forces excluded men iflith ulcer histories but, despite this pre-
caution, more than 77,000 servicemen developed ulcers. Over u8,000 were
separated from the service as a result of ulcer disabilities, adding greatly
to the national economic burden through subsequent pensions.
Some of the most important contributions to the treatment of peptic
ulcer have been made by grantees of this program through application of
knowledge gaiiied in basic studies. Tliree grantee surgeons at the University
of Chicago, University of r4innesota, and the University of Washington, have
developed a variety of new or combination operations designed to meet the
different needs of individual patients. These include improved methods of
cutting the nerves to the stomach, removal of the acid-secreting portion of
the stomach, and several new ways of connecting the stomach to the intestine.
The mortality from gastric surgery has been reduced, and many of the post-
surgical complications have been eliminated. Other grantees are devoting
their efforts to the development of better methods of drug therapy for the
Diseases of the reproductive tract . The diseases of the reproductive
tract are numerous and varied. Iferor such diseases result in sterility, a
condition which adds to the heartaches of childless couples. Research has
already shown that some of the diseases and conditions causing sterility
may be remedied or prevented, but much remains to be done, especially at
the fundamental level. An example of the work supported by the general
research grants program in this area is research at the University of
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Pennsylvania concerned with the biocher.dcal changes taking place iir.tnediately
Toxicology . The problems in toxicology become greater iivith every
passing day. Thousands of new chemical compounds are being put to use in
increasing amounts in drugs, food, cosmetics, houbehold supplies, and in
agricultural and industrial chemicals. Unfortunately, many of these new
compounds have been found to be toxic to manj the detrimental effects of
others are not yet knovm. Some of our grantees are attacking segments of
the problem. For example, at Utah State Agricultural College, studies are
under way to determine the histological changes iri tissues of animals fed
different insecticides. This is particularly inportant because of the wide-
spread use of new insecticidal poisons v/hich are constantly coming onto the
market. If it is demonstrated that harmful residues retrain in animal tissues
vrhich are later consumed as food products by man, a definite public health
hazard may develop.
Diseases of the skin . Diseases of the skin receive amazingly little
attention in view of their importance. Many severe dermatological conditions
are caused by bacterial or fungal -infections and a tremendous amount of money
has been expended in the preparation and use of superficial medicaments to
counteract these disease manifestations. As a consequence, expert derma-
tologists cite that nearly half their patients — estimated in the hundreds
of thousands yearly — are those who seek relief from conditions caused by the
unwarranted use of preparations purported to relieve itching, to cure bacterial
or fungal infections, or to reduce inflammation of the human skin. Yet very
little is known about the precise cellular mechanisms involved in sensitization
of the skin induced by topical application of medicines vrhich are in widespread
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use. Because of its thin structure, the skin is very difficult to study.
Microtechniques have recently been developed, hovfever, which v;-ill at last
permit controlled studies. If additional raanpovrer can be trained and new
centers of skin investigation encouraged, there is good reason to hope for
an accelerated rate of advance in this important area.
Public health and preventive medici ne. Medical research tends to be
oriented tovirard the specific disease and the management of the ill individual.
Yet to achieve maximum improvements in the health of the Nation, methods must
be developed to meet the problems of preventive medicine at the community
level. This oftien calls for an entirely different approach and it is the
responsibility of the Division of Research Grants ' program to support and
stimulate research of this sort. From a research standpoint, many diffi-
culties are presented because methods for community studies are largely
undeveloped. Steps are being taken to overcome these difficulties in some
areas j for example, in the noasurement of community morbidity.
In California a grant-supported survey conducted by the State Depart-
ment of Public Health has developed a household interview method which can
accurately determine the extent of chronic illness in a limited area. This
method is now being applied in a state-wide sampling survey which v/ill pro-
vide California with information basic to the operation of its health program
and other States with a technique vfhich can be applied elsewhere.
The entire field of public health is undergoing revolutionary changes
related to the shifting picture of illness in a community. Public Health
personnel, trained primarily to control the epidemic diseases, arc confronted
increasingly with community problems in the prevention of degenerative and
chronic diseases afflicting the aging population. One of bhw great research
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challenges today is the rapid deTelopment of means for translating kn.owledge
of disease in the indi-vldual to methods of prevention at the comnitmitgr level.
SPECIAL IRROBESM AREAS
Increases are requested for two specific areas of research? additional
work in water pollution (for which $1,000,000 is requested), and iraproved
utilization of nurses (for which $62.'5jOOO is requested), Applicatior© for
support of research in these two special fields must, as is true of all
Pu-bli-c Health Service research grants, be recommended for approval by a
Special research program on water pollution . An ample suppljr cf
water of good and safe quality is essential to community health and well-
being, especially to domestic living and to the industrial activity which
is the basis for community livelihood. Great expansions in urban popula-
tions and industries have steadily increased demands for water, and at
the same time have greatly increased the discharge of waste materials to
streams which fuj^nish our raw water supplies. With a continually expanding
econon55r, it has become apparent, in more and more areas, that only by re-
peated reuse of water can the anticipated future needs be met. This means
that waste discharges— both from the home and from industry—must be treated
to remove polluting materials before being discharged to streams. Thus,
the water in the streams can be vsed over and over as it flows from city
to city and from industry to industry.
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Tho technical complexities of v;astc treatment are continually
compounded not only by the increasing voluracs of scvragc and industrial
T/astcs but also by nciv types of rrastc materials, particularly from tho
mushrooming chemical industry. The manufacture of thousands of neiv
synthetic chemicals is introducing into our v/atcrcourscs more and more
Tfastc compounds v;hosc effects on aquatic life, on human beings, and on
sewage and T;atcr treatment methods aro but slightly understood. Methods
for removing these substances from irastcs or from streams have generally
not been dovclopod and, moreover, methods arc not even yet available for
detecting and collecting them for analysis and study#
A review of tho research projects previously supported by the Public
Health Service illustrates some of tho research attempts that arc being made
and tho need for a much greater effort for solving those problems, Tho
object of such research is to provide tho basic knowledge v/hich vail permit
communities and industries to proceed, within their own financial resources,
vath the design and construction of tho necessary v;aste treatment works»
Scientists at sixteen institutions throughout the country aro engaged
in research on sewage contamination and sewage disposal methods. Large
amounts of scvragc and wastes are still discharged iiithout any or only
superficial treatment into surface waters. Such an instance is the area
of Biscaync Bay, Florida, Trficrc investigators have been carefully measuring
tho deleterious effects of such discharge on the marine life and the degree
to T/hich tho water is rendered unfit for human use* The design for the
scv/ago plant nov/ contemplated for this area will incorporate features based
on some of the findings developed under research grant projects at tho
Massachusetts Institute of Technology, tho liiivcrsity of Colorado, and
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Another important problem area is that of modifying or improving the
efficiency of existing methods of SGwagc treatment so that existing plants
may be adapted to treat larger quantities of r/astes, or to remove ncvrcr types
of materials which would be deleterious to dovmstream users, or to continue
to function despite the prcscnco of specific -waste materials v/hich interfere
vdth conventional treatment plant operations. The trickling filter method
and the activated sludge method, for example, are being studied under
Another type of research investigation shovdng real promise is that
loading to the development of new and more economical methods of sewage
and vrasto treatment, A research grant project at the University of
California, for example, has developed fiindamcntal data on the related or
symbiotic effects of algae and bacteria in the treatment of soTrago by ponding.
Those data indicate that such ponds can be reduced in size and at the sane
time operated under controlled conditions to produce a highly purified
effluent and may oven be adapted to mass algal culturing to recover the
valuable fixed nitrogen present in ^Tastes in the form of a highly nutritious
Intensified research is needed also to study the viability and
destruction of pathogenic bacteria and other harmful microorganisms \ihcn
these pass through treatment plants, or arc discharged to streams or arc
percolated into the ground, or when disposed of by irrigation, Yorkers of
the Kansas State Board of Healthy for example, have shoivn that the histo-
plasma fungus is not removed by the conventional flocculation and filtration
procGsscs v;hich are the basis for most modem filter plant design. Also,
the Nov; York State Department of Health has done v:ork loading to the
dovolopmcnt of a now method for the quick nnd accurate identification of
TiTascri in vratoro
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The proposed research grants program in Virater pollution control,
coupled mth the stimiilatory activities of the Taft Sanitary Engineering
Center at Cincinnati, vdll periTiit the Public Health Service to provide the
nucleii of new findings essential for mobilizing the national resources to
a comprehensive approach to th6 serious and grov/ing problem of vrater
Research on improved nuj?se utilization . Nursing service is essential
for the conduct of modern medical programs both preventive and curative.
It is well known that the demahds for nursing service exceed the present
supply. It is not expected that this demand can be met through an increase
in number of professional nurses. Ways must therefore be found to render
more effective service vdth the present supply.
Research into nursing and its management can develop new methods
which will reduce the gap in seol'vices. For exaiAple, a recent research
study involving both nurses and doctors experimented with different nursing
methods. Certain ones v/ere found to be far superior to others in speeding
patient recovery. A few studies like this and researches on management of
nursing services have yielded proniising results, Hov/ever, only a beginning
has been made.
Nurses of today must keep pace vdth the dramatic advances in medicine.
Modern nurses care for heart and brain surgery cases and must knov; care and
rehabilitation techniques for the long term chronic patient. They must be
able to predict and manage the behavior of the psychiktric patient. Nurses
must be able to fit into team operatioh but also be able to act independently.
Research is needed to develop improved methods of meeting patients' needs and
to determine how nurses are to be prepared for their grovang responsibilities.
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Practical nurses and nursing aides combine r/ith professional nurses
in supplying nursing services needed in hospitals, yet only one-sixth of
the practical nurses and a very small percentage of the nursing aides have
had training for their duties. Studies are needed to determine the proper
training of these groups so that they can liberate professional nurses for
responsibilities requiring more complex skills and judgment. Studies are
also needed on the most economical and best way of administering this
diverse group of nursing personnel so that patients -will get safe care
and hospital finances avill be conserved.
Nurses in managerial and teaching positions everywhere are
strategically placed to implement the findings of research. Training for
these positions should provide knowledge and skill necessary for applying
research results. Increasing the number of these trainees is another factor
in the solution of the shortage problerA and the value of this factor will be
enhanced by an active research program.
All types of nursing research require nurses -vvho are trained in
research techniques. Relatively few nurses now knovt those techniques. Con-
centrated training in research can prepare a larger number of them to
conduct needed studies*
The problems of nursing urgently need study and research. The
proposed program will enable universities and other institutions to under-
take needed researches. Findings will alter nursing practice and vdll affect
the comfort and recovery of millions of people in hospitals, clinics, and
SUMvIARY OF 19^6 PIANS
In 1956 the Division of Research Grants' program vdll continue to
support exploration of ideas in fundamental, clinical, and public health
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areas, and rail devote particular efforts to stinulate added research in
the selected fields. Special attention vdll bo given to the prcbla'ns of
diseases of the skin, to studies of human embryology and early dcvolopmcnt,
to the problems of vrater pollution, and to research directed tovrard
provision of more adequate nursing services*
Dr, Flqjrd S. Daft
Director, National Institute of Arthritis and Metabolic Diseases
National Institutes of Health
Public H3alth Service
COMMITTEE ON APPROPRIATIONS
"Arthritis and Metabolic Disease Activit:|es"
Mr, Chairman and Members of the Committee;
Although the National Institute of Arthritis and Metabolic
Diseases is one of the yoimgest of the National Institutes of
Health, it is comprised in part of some of the oldest and most
productive research laboratories in the Public Health Service.
The Institute was es-^.ablished in 1950 under the provisions of
Public Law 692, which alst directed that it absorb the program
of the former Experimental Biology and Medicine Institute, It
conducts a broad program of laboratory research and clinical
investigations, and supports research and research training
through grants and awards.
The first direct appropriation for activities of the
Arthritis and Metabolic Diseases Institute was in 1952, when
nearly four million dollars were made 0,vailsl)lo<, Tii©
Congress has continued to increase support of this program with
each successive year — approximately four and one-half million
dollars in 1953, seven million dollars in 195u, and more than
eight million dollars in 1955* The Institute has now developed
a well-rounded attack, both upon the broad spectrum of chronic
diseases in thj.s area and upon basic laboratory studies related
to these conditions.
This is but the fourth time that the National Institute of Arthritis
and Metabolic Diseases has been privileged to appear before this Committee
and discuss its programs and its progress with you.
ihe relative youth of this Institute is not reflected in
its internal structureo When we were formed by an Act of
Congress in 19$0f it was our ;ood fortune to acquire a number
of long~established laboratories whi/ah f or many years had been
making distinguished contributions to medical science in such
fields as nutrition;, pathology, pharmacology, chemistrj', and - .
physical biology* Thus at the same time as the Institute
acquired identity, it also acquired a souno. base of fundaraental
studies upon which its program of clinical investigations could
Research interest in arthritis and the metabolic disorders
is of comparatively recent origin..* In medical science, research
interest usually is associated with research opportunity* It
follovjs that the time must b, ripe for significant advances in
this field* The accoiaplishiaents since the establishment of the
Institute in 19^' demonstrate tht validity O- this hj^othesis*
The groi'fth oi public and professional interest i.i ^thritis
rheumatism, and related disorders has folla^jed an intersting pat-
tern* In 19l;6, only abou':. O50>000 was spent in rheura::tic disease '
research) there were fei: scientists interested in the field, only
a handfvl o_ artliritis clinics, and ■d.rtually no opportiinities for
specialized research training* Th. n tMags began to happen with
drai.iatic suddenness* In l^UJ, th-^ Arthritis aix! Rheumatism Foun-
dation was established to suppor o research, public education^ and
service* In 19U9, liench and Kendall o.. the ilayo Clinic made their
revolutionary announcement of the effectiveness o2 cortisone and
ACTH in suppressinc arthritis* In 19^0^ Ih^ .atical Institute of
Arthritis and ..eta'.-'olic Diseases was created* These developments,
both private and public^ set the sta£;e fo:-- prpgress* :lni there have
bo^i more ac'vances in the last five years than bhere were i.i the
preceding five hundred.
Diseases with ii?ldch th» Institute is Concerned
Heart disease, cancer, anc': mental illness arc O- covrse kncrwn to
be families o, diseases, an no':, single disease entities in themselves*
Tho members of the family become more numerous anc ;.he relationships
more complex when one atte..'.pts .0 describe tho f\:ll range of diseases
an disorders encompassed in the fields of interest O- the rational
Institute of Artliritis anc . etal.'olic Diseases. Yet there is ample
reason for groupinc: them to:;,-ther for a unified research effort, for
they ha.e much in coi.imon*
Ohv. major category 0.. diseases vdth which we are concerned can be
called th^ rheumatic disorders* They a, e characterized by pain and
stiffness in joints and muscles^ often res'-dting in swelling and
inflammatioii Li th. affected areas» In the several forms of
artliritis (rheumatoid artliritis, osteoartliritis, and gout)j tlae joints
themselves are affected* '.vhen the rheumatic disease is located in the
connective tissue^ particularly around joints, muscles, and tendons
(as in fibrositis, bursitis, neuralgia, lumbago, or sciatica), it is
called non-articular rheuinatism* A tl ird group of rheumatic disorders
is called the collagen jdigeaseSjj i^ which the c^nnectivs tissue is
attacked, inflamed, and e.' ■ a destroj'-ed. These diseases bear esSterio
names -- lupus erythematosus, scler'^derma, polyarteritis nodosa,
deriTiatomyositis t— but they ar^ serious and often fatal disorders.
The second major category of diseases to which this Institute
gives special attention are the metabolic disorders. In this family
of diseases, the similarity is in the defect cr deficiency in the
complex biochemical processes by which the body "metabolizes" f-^od,
air, and water, converting them, into the growth and energy which
maintain body structure and function. The research problem here
has to do essentially x-jith hormones, enzymes, and vitarains — the
great classes of corapoui'ids invnlved in the control of m^etabolism in
the body. Diabetes is perhaps the most inportant of the metabolic
diseases; and the defect there, for example, is the inability of the
body to utilize sugar properly because of the absence rr improper
f'inctioning of a hormone of the pancreas called insulin. Other diseases
in this group are cirrhosis of the liver, peptic ulcer, the anemias,
•steoporosis, and other conditions, Anpther kind of metabolic disorder
results from deficiencies or excesses in diet — either primary deficiencies,
faulty absorption of nutrients, poor utilization of nutrients, or special
dietary needs resulting from disease, trauma, surgery, or other stress.
Included in this group are deficiency diseases such as beri beri and
pellagra^ mineral deficiencies such as secondary anem.ia and goiter, stunted
growth in children; pernicious anemia, sprue and the inegaloblastic aj^emias
of Infancy =aiid pregnancy j' and obesity— perhaps the nost important number ' *
of this gtovp becaiise of its relation to such diseases as diabetes, »"'« •'
arthritis, heart disease, and certain forms of cancer.
Thus the areas of research interest T:ith -ijhich the National Institute
of Arthritis and Iletabolic iJiseases is directly concerned impinge on
virtually everj'" disease of :vian. It is of particular value, then, for this
Institute to be set in a total research environ:ient which encourages a
maximum amount of interplay between its scientists and those of the other
'The Human and jiicononic Burden
Since the diseases related to the tfork of the National Institute o£
Arthritis and Iletabolic Diseases are so diverse, consisting largely of
conditions which are more incapacitating than fatal, it is difficult to
get an accurate assessment of their current status as health factors
among the American population. Our best estiiriate is that roughly 2Sp
of the people are directly affected. The economic burden has been
estimated to ar^proach one billion dollars a year.
lie can be more spejcif ic, however, in assessing some of the major
disease entities, '% Icno': that arthritis and the related rheuraatic
disorders cripple and incapacitate more people than ary other chronic
illness in this country. Today, more than ten million suffer the painful
torments of these conditions. Of these ten million, approxii'.iately one ...
million are perr.ianently disabled, unable to earn a living and thus a
hea"vy economic burden upon their families, their communities, and the
Nation as a whole, Rheianatoid arthritis, the ^nost vicious of the
rheujnatic diseases, is knoim as the great crippler; it is responsible
for the disability and economic loss among people in their most pro-
I'Je knox-r that about 2^,000 people die each year from diabetes, and
that 25>000 more die of complications brought on by the disease. Approx-
imately two million people in the United States are afflicted with
diabetes J nearly half of these have the disease in a relatively mild
form, and the symptoms go unrecognized, tut diabetes has an insidious
and alanning way of creeping up on its vic;:feiras and catching them
unaware. Diabetes is hereditary, and diahetics are livinr longer
because of insulin, so the disease continues to increase in incidence*
Statistics of this kind are staggering and somewhat depressing.
The hope for progress lies in a many-faceted orogram that extends across
the full range of research, training, medical -.iractice, and pu.hlic
education. The Federal Government's part in such a program is centered
in the '"ublic Health Service, X'Tith certain control and education
functions vested in the Bureau of State Services, and Tiith research and
training as the primary interests of the National Institute of Arthritis
and Metabolic Diseases,
The last four years have seen the Institute grow in size, broaden
in scope, improve in coonerative relationships, and increase in scien*
tific productivity, ■ e have been unusually fortunate in securing out-
standing professional staff in key positions throughout the Institute as
our program has extended into new areas.
I would like to cite particularly Dr. DeWitt Stetten, who left The
Public Health Research Institute of the City of Mew York, Inc. to become
Scientific Director of the Institute, Dr. Stetten is internationally
known for his research contributions, particularly in the fields of
diabetes and metabolism. Our Clinical Director is Dr. Joseph J, Bunim
widely recognized for his talented and perceptive applications of
fundamental knowledge to clinical investigations in the rheumatic and
This Committee, which has played such an active role in the estab-
lishment and support of our Institute, will be interested in some of the
acconplishments of the past few years, I am pleased to have this
opportunity to report back to you that significant progress is being
made, both in our direct research operations at Bethesda and under the
extensive program of research projects supported by grants from the
Progress Against Rheumatic Disease
One of the most significant and exciting medical discoveries of 1951;
was announced in November by clinical investigators of the Institute at
a scientific meeting of the American Rheumatism Association held at the
National Institutes of Health Clinical Center,
Two new drugs, metacortandralone and metacortandracin, had been
tested in Clinical Center patients with rheumatoid arthritis, and were
reported to be more effective than any other drugs known, including
cortisone and hydrocortisone. The nex^^ conpounds, developed by a
pharmaceutical house, had previously been tried only on animals.
Metacortandralone was tested in a series of seven carefully-
selected patients ~ six women and one man, ranging in age from 16 to
67 years. The duration of the arthritis in these people ranged from
2|- to 2$ years. Prior to this trial, three of the patients had been
treated only with aspirin, while the other four had received just about
every type of recognized treatment, including cortisone, hydrocortisone,
corticotropin (ACTH), phenylbutazone, and gold conqjounds. In no case
had previous treatment produced adeqxxate response, and in three there
had been serious, objectionable side-effects.
The response of these patients to the new treatment was prorpt,
positive, and consistent. Each improved rapidly, both objectively and
subjectively. The second of the drugs, metacortandracin, produced
equally good results in another series of patients.
It is highly significant that neither of the nevr drugs, though
four times as potent as cortisone, produced in any commensurate degree
the undesirable side-effects so often associated with cortisone,
hydrocortisone, and corticotropin.
Neither of these new drugs can be regarded as a cure for arthritis.
Although they provide what now seems a much more effective and safer
therapy than any previously known, only long-term use will tell the
final tale. Other medical research institutions, since our original
announcement, have been subjecting the drugs to additional trials, and
our own clinical investigations are continuing. Results to date confirm
our original conclusions.
other Advances. Not only have advances been made in the treatment
of arthritis, but also in our I'nox-rled^e of the associated aneiuia, the
activity of steroid hormones in the body, and other areas basio to our
understanding of the rheumatic diseases.
Many patients with rheumatoid arthritis have an associated anemia
which is resistant to the usual methods of treatment. Radioactive
isotopes, used to tag red blood cells of patients, have enabled Institute
scientists to make important determinations concerning this condition.
It has been found to result from an increase in red cell destruction
plus a failure of the bone marrow to produce sufficient red cells to
compensate. These findings should lead to measures for more successful
treatment, increasing the resistance and stardina of artliritis patients.
In another study small amounts of radioactive cortisone and
hydrocortisone have been administered to animals and human subjects
so that the body's distribution and disposal of these hormones could
be accuratelj'" determined. Information has been obtained that will
help us understand how these drugs act in rheiimatoid arthritis and
Institute investigators have found also that growth hormone and
thyroid hormone profoundly affect the production of collagen, an
important constituent of connective tissue, which in turn composes the
supporting structure of the body. Since abnormalities of the
connective tissue are known to occur in rheumatic diseases, this
finding has an interesting relation to the arthritis problem.
A significant development at the Medical Colle're of Alabama,
3irrain';tham, by scientists supported through an Institute grant, is a
new teclinique by which they can obtain adequate quantities of normal
Icnee joint fluid to enable them to make tests and coiiparisons. In the
course of this study, a substance has been found in normal knee joint
fluid which is not present in fluids from abnormal joints — a protein
fraction. The study is continuing in an effort to find out why this
fraction disappears when the joint is diseased, uhat happens to "it,,
and when and wliy. The results may well answer many questions concerning
possible causes of rheumatic disease.
Progress Against Metabolic Dis_eases
Less spectacular but significant progress has been made in the
field of diabetes. Although the cause of diabetes is far from
comiDletely understood, heredity is kno^m to play a role in predisposing
individuals to the disease, and obesitj'" is a major factor in its
Another important aspect of diabetes is the multiplicity of
disorders that accompany it, such as arteriosclerosis, Tliis seems to
develop prematurely in the diabetic population. Other frequent
con^xlications are gangrene of the extremities, which leads to
amputations; disease of the smaller blood vessels, particularly in
the retina, which leads to blindness; and kidney disease, leading to
failure of this organ. Long-term studies with a view to better under-
standing and control of these serious complications are continuing
under our grant program.
The action of insulin must also be understood in order to make
better pro-^ress a'^ainst diabetes* Important studies in this area are
under way at the University of Pennsylvania and the University of
Chicago, both supported by .grants from this Institute, Significant
progress is being made, Attacliment of the hormone, insulin, to body
tisr;ues has been demonstrated, and the activity of the attached hormone
has been measured. It has also been demonstrated that insulin affects
the ease with which sugar crosses cell membranes. Both of these
discoveries aid in luiderstanding the role of insulin in the body.
In the course of chemical and biological studies of insulin, a
contaiTiinant was encountered that has since been shown to arise in cells
intimately associated td.th those that produce insulin itself. This
substance, glucagon, is itself active in the regulation of sugar
metabolism, although chemically unrelated to insulin. It appears to
provoke a rise in blood sugar at the escpense of the sugar reserve,
glycogen, of the liver. The role of glucagon in diabetes, and
especially in the vascular complications of diabetes, is a subject of
study by Institute grantees.
The demonstration of insulin antagonists in the blood of some
diabetic patients lias stimulated studies of the chemical nature and
origin of such agents. Little is knox-m of these substances at present,
but numerous suggestive leads are being follot^fed. Since the antagonists
are causative agents of clinical diabetes, it is obviously imjoortant to
learn as much about them as possible.
Other Metabolic Diseases . It was mentioned last year that studies
are under way at the University of Utah on inherited metabolic defects
leading to imbecility in infants. These are long-term studies that will
require many years, but another important advance has been made in our
understanding of the abnormalities of protein metabolism that accompany
or underlie this group of diseases. It now appears that two amino
acids, so-called building blocks of protein, are not metabolized
normally in infants with this metabolic disorder. The amino acids
involved are phenylalanine and tryptophan.
In our endeavor to understand and combat metabolic diseases, we
must advance our knowledge of the basic chemistry of the body. For
example, we must determine the steps by which food materials are broken
down and rebuilt into needed substances. This information must be
gathered first from normal animals and subjects, and must then be
compared with analogous information from animals and patients with
It was long thought, for exanple, that sugars are broken down in
the body in one way only, A major advance in recent years has been the
discovery, principally by investigators at the National Institute of
Arthritis and Metabolic Diseases, of a second pathway of glucose
metabolism. Interestingly enough, the process appears to involve some
chemical reactions which are the reverse of those occurring in photo-
Another major advance, by scientists of the Institute and other
research centers, is the discovery of steps in the synthesis of
mucopolysaccharides. Abnormalities in this group of compounds appear
to be basic to arthritis and other rheumatic diseases. Enzyme systems
involving a newly discovered substance, uridine triphosphate, have
been delineated, and some of the synthetic steps by which the body
builds constituents of normal mucopolysaccharides have been precisely
Still another promising field of basic research in metabolism
relates to nucleic acids, essential components of the genes. This
research area is therefore fundamental to our understanding of all
hereditary metabolic disorders. During the past year, and a few years
preceding, notable discoveries have been made in this field both at
the Institute and elsewhere. As a result, we are on the road to
understanding the chemistry of the nucleic acids and the metabolic
processes by which they are formed in the body.
It is with real pride that we report the advances in fundamental
knowledge resulting from these fundamental studies. They have no
immediate application in clinical medicine, but they constitute the
firm foundation upon which the seemingly spectacular clinical
advances of tomorrow will be based.
Significant Program Developments
As previously stated, one of the Institute's major efforts during
the past fiscal year has been the clinical study of two new drugs,
most promising against rheumatoid arthritis. These drugs must now be
evaluated in related rheumatic diseases. Moreover, the demonstration
that steroids superior to cortisone and hydrooortison&' can be
«?,fpr<a'ir- nt b-:
prepared indicates that many other new conpounds will become available,
¥e hope to continue the clinical testing of such compounds. At the
same time our fundamental studies in the field of rheumatic diseases
will be continued.
A part of the increase in the 1955 appropriation for research in
our laboratories was utilized to augment studies on diabetes and related
metabolic disorders. Laboratory and clinical studies of hormonal and
nutritional factors, and the relation of metabolic mechanisms to the
clinical state, have been inaugurated, and new and expanded studies are
planned for this year, A new clinical branch on diabetes and endocrinology
has been organized and is being further staffed.
Effective use has been made of the funds appropriated by Congress
for research grants in fiscal year 1955. The support of promising research
projects in diabetes and other metabolic disorders has increased
substantially. During the coming fiscal year, we plan to assist ad-
ditional worthwhile projects in this area, and to support to the fullest
possible extent the clinical testing of new drugs in arthritis. Standing
as we do at the threshold of major clinical victories against arthritis
and related rheumatic diseases, it is inperative that forthcoming drugs
be evaluated as rapidly as possible.
A new program under way is designed to solve some of the problems
of postgraduate training in arthritis, diabetes, and other metabolic
disorders. Specialists in arthritis have long recognized a desperate
need for the training of additional medical personnel in this area.
i.j'^fKi v' U<M!«Li^' Xi\i
There are only 800 to 900 qualified physicians particiilarly interested
in the treatment of this disease, as attested by their membership in
the American Rheumatism Association. Needed almost as urgently is
postgraduate training in diabetes and other metabolic disorders. In
recognition of the seriousness of this situation, a portion of our
traineeship funds is being used to make a small start in a program of
training grants to institutions. The response to the announcement of
this program has been enthusiastic and speaks strongly of the needs in
The American Rheumatism Association held its First Interim Session
at the National Institutes of Health in November, 195ii« This was in
addition to the Association's regular annual meeting, and was
necessitated by the much increased interest in this important field.
The meeting was highly successful, and arrangements have been completed
for a Second Interim Session at the National Institutes of Health in
the fall of 19?5, This is only one of many ways in which the National
Institute of Arthritis and Metabolic Diseases is working with appropriate
professional and voluntary organizations to further research training
and the clinical application of new knowledge in arthritis, diabetes,
and other metabolic disorders.
There has never been better justification for intensified effort in
research on the rheumatic and metabolic diseases.
'fro '*"!B ^'ririT
.» g<ai«T;;>n.^ .dOi'/Tr
During the past year, with the discovery of the remarkable effective-
ness of two new steroids in arthritis, another milestone has been es-
tablished in the march of medicine toward the control and cure of a major
This breakthrough opens new vistas looking toward success in this
field. The new steroids point the way, and we can look forward confidently
to even better antirheumatic agents in the near future.
Today we stand upon a rapidly broadening base of fundamental
knowledge, with major roadmarks established. We are convinced that
the path of research in the rheumatic and metabolic diseases was never
as brilliantly lighted, and that the time has come when intensified
research effort will pay off with major gains.
rl&t.-r ,~f-*y- .'
Dr. John B.. Heller, Jr.
Director, Na.tional C^ncer Institute
Pal3lic Health Service
COMMITTEE OK APPHOPRIATIONS
Salaries, Expenses, and Grants, National Cancer Institute
Mr. Chairuan and Meuters of the Cor.uiittee;
The National Cancer Institute was established "by Act of
Congress of Au^st 5» 1937 > for the purpose of achieving
control of cancer in rnan throxu^i studios relating to the
cause, diagnosis, and treatnent of neoplastic diseases, and "by
supporting useful application of the results of such studies.
Although cancer research has expanded nost rapidly
since the end of World War II, the Public Health Service has
been active in the field since 1922. At that tiuo cancer
research within the Public Health Service was initiated by
two groups of scientists - one at Harvard University and the
other at the Hygienic Laboratory in Washington. These groups
were nerged to form the nucleus of the N ^tional Cancer
Institute. Under authority of the organic act of 1937. the
chief provisions of v/hich wqro incorporated in Public La-w ^+10,
the work of the Institute is divided into two broad areas of
activity - tho acquisition of knowledge about cancer, and the
dissenination and application of such knowledge. In the first
area, the Institute conducts original research, both b.sic and
clinical, in its ov/n laboratories; supports research by
individuals in other institutions and organizations through
grants-in-aid; and helps enlarge the supuly of q.ua.lified
research investigators by awarding follov;ships to promising
young scientists. To secure the widest possible dissenination and
application of cancor knowledge so a,cquired, the Institute provides
for grants, consultations, and denonst rat ions within the States;
provides teaching grants to approved professional schools of
nedicine, dentistry, and osteopathy; awards tra,ineoships to young
clinicians; and distributes professional ?.nd lay educational and
i nf r nat i nal uat e r i al s .
■'j.'.i,'0''!v .".':i:; ■ •
•t ^CV;J. i'.
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National statistics suggest that on this very day approximately 650
people will die from cancer. The cancer death toll is rising. Because
I know we all share great concern over this situation, I consider it hoth
a pleasure and an opportunity to discuss with you not only the programs
and problems involved in the government's fight against cancer, tut also some
of the strategic gains made in this struggle. Progress from year to year
in this field of medical research is relatively slow, and the gains that
are made are seldom spectacular, Taut I can assure you that accomplishments
of very real value have "been achieved, not only in the lahoratory but also
in the area of direct control of this disease in the population.
EXTENT 01 CANCER
I should like again to refer to the extent of the cancer problem on
the basis of our latest statistical information. Cancer is unquestionably
a major public health problem. In 1955 about 235iOOO persons will die of
cancer. A-bout three quarters of a million will be under treatment, of v/hom
550,000 will represent newly diagnosed cases. If prevailing incidence rates
contintie, some 1,000,000 persons v;ill be receivinf.^ treatment annually for
cancer by 1975. Why? Primarily because half of all cancer patients are
between 50 and 70 years of age, and 'iur population is growing older.
Unless the cancer death rate for older people can be cut drastically, the
number of persons affected by this disease will increase by 50 percent
in the next 25 years.
Another factor must be considered. Ca,nccr is the second leading
cause of death in the formative years of life, between 5 and l4. The
postwar baby boom has sent the birth rate up steadily, thereby enlarging
this age group in the cancer picture.
■•n \-:%*.'V ic>
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The economic loss due to cancer is staggering on two counts: the
drain on the family's financial resources is tremendous over a long
period; and millions of man~hours of work are lost, involving many more
millions of dollars? worth of product and skills. Snail wondor, thon,
that cancer is described as a "catastrophic" illness.
With the Committee's permission I will discuss the future plans
and needs of the National Cancer Institute in the light of some of the
major accomplishments under our program during the past year*
The ultimate goal of cancer research is to discover the hasic nature
of cancer in man in order to esta.hlish means of preventing and curing ito
Eut cancer is no simple disease which alv/ays exhibits the same symptoms.
There may "be as many different kinds of cancer as there are parts of the
"body where cancer may occur. The disease is not always recognizable for
what it is until late stages of development. Symptoms vary among types and
locations in the tody. As of this date, medical science knows of no one
basic cause or cure of cancer.
This variability of laalignancy is what makes cancer research imiq.ue.
Cancer is a disease of the cell. Medical science is working at the lock
to the cell with increasing expertness, and when the key is found which
opens it and discloses the nature of the mystery , we may be very close to
full knowledge of the fundamentals of life. Major research eraphasis at
present is placed on basic questions concerned with the chemistry and biology
of growth itself, because it is believed thiit increased knowledge of growth
phenomena can load to more rational approaches to the cancer problem than
is now possible.
- /+ -
A large part of our research program seeks to extend knowledge of
the causes of the large group of related diseases included in the term
"cancer," the nature of the transformation of cells from normal to cancerous,
and the iDiological and "biochemical differences "between cancerous and normal
cells which may "be exploited for therapeutic purposes*
Cancer research is not without its successes, though we have jrot to
reach "paydirt" In terms of the causes of cancer. Radiation techniques and
instrximents tmknown ten and fifteen years ago are conmonplace today ~ and
are snatching cancer sufferers frop death. Chemicals of un"believable
complexity are serving magnificently as palliatives ~ and are easing pain,
increasing the effectiveness of surgery, and prolonging life. Hew
diagnostic tests now on trial are discovering cancer of the uterus in the
earliest stages - and giving long life and extended motherhood to many women.
Knowledge of the nature and extent of cancer as a disease in the
population is essential to a general plan of attack on the pro"blem involving
la'boratory research and direct control measures. Data on prevalence,
incidence, distri"bution, and mortality from cancer in human populations, and
estimates of the influences of such factors as geography, environment, and
race, are o"btained through epidemiological studies. In this field the
National Cancer Institute has completed the total ta"bulation of data
gathered in its studies of cancer illness in ten metropolitan areas which
were initially surveyed in 1937-39 and rosurveyod in 1948-'4-9» This project
is considered "by research authorities throughout the world as the most
comprehensive of its kind ever conducted. Certain hypotheses as to the
extent and nature of cancer have "been corro'borated and distur"bing trends
'■ bar fitxr.r. "io ff?.---
.■ iO'tillQO ^Oii'ikb bin
Among the significant findings produced by this study are; (1) that
the cancer death rate in the Nation's white population is definitely higher
for men than for women, constituting a reversal of the relationship which
had existed until recent years; (2) that the chance of developing cancer is
a"bout one-third greater for white persons living in the South and the West
than for those living in the Northj and (3) that there has "been a sharp
increase in lung cancer generally; and (^) that lung cancer is to be found
four times as frequently among men as among women-.
In cooperation with the Veterans Administration, some 3C0,C00 World
War I veterans holding government life insurance are being asked to fill
out a detailed questionnaire which includes information on their smoking
habits « Response has been dramatic. Replies have been received from over
200,000 so far, and the data are being processed. It should be possible
thereby to calculate more reliable rates of the incidence and mortality
from lung cancer among smokers and nonsmokers than are now available-.
The American Cancer Society is also greatly interested in this
problem, and is conducting a S-year study of the smoking habits of 200,000
men over 50 years of age to establish a connection, if any, between smoking
and lung cancer. Information on the cause of death in the 5»000 deaths
expected each year in the group is being recorded^
En vironmental-Occu pat ional Cancer
Certain questions logically suggest themselves in the light of
information about why people of different types, living in different localities
or under different conditions, get cancer e
A number of substances or compounds are known to bo carcinogenic oi*
cancer-causing. Most of them are found in industry - some tars, certain
petroleum products, radioactive materials, some chemicals involved in metal
■ '1 ' '
^ ■ '•
• ■<-.-> , . '
- 6 -
snelting processes, and other products of industrial activity. Froa such,
findings it has "been possible to prevent harcif-ul exposure of the industrial
worker in the handling of these materials.
The Institute is vigorously pursuing a series of investigations in
environnental and occupational cancer.
Anong aany netals examined and analyzed in the laboratory, nickel
and possibly chroniun have "been found to he carcinogenic. It is possible
that in these cases the cancer-causing nechanism nay he related to reactions
between "body proteins and such notallic dust when inhaled. It has also "been
ahown this past year that certain oils used as petroleun substitutes (such
as shale oil) possess some cancer-prodticing products. At the sane tine
extensive studies of air pollutants are being made to determine their role
in causing lung cancer.
A general health survey is under way of workers esqposed to radiation
and other hazards in the new uranium mining industry of the Colorado
plateau. These miners are exposed to radioactivity present in the sineral
dust. Study is being made of the effects of such contact and inl'.alation,
and the type and incidence of cancers that develop.
The Institute is also engaged in the study of the carcinogenic or
cancer-causing potential of tobacco. In one project, the purpose was to
determine the frequency of respiratory cancer among workers engaged in
the processing and handling of tobacco materials in the manufacture of
cigarettes. A major finding of this study was the close approximation of
cancer mortality among these workers with that of the total population of
the two States involved.
There is no more important field in cancer research than that of
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■biochemistry, which is concerned with the deternination of differences in
the chemistry and netatolisn of normal and cancer cells. Basic research
is teing performed on proteins, which are essential to life and on peptides
and amino acids, v/hich are important components of protein. Particular
attention is given to enzymes, which are proteins that selectively control
most of life's processes. Another area of investigation is that of
carcinogenesis, or the study of what causes norma.1 cells to hecome cancerous.
A third area deals with hormonal influences or carhohydrate metabolism.
The reported increase of peptides in the "blood of cancer patients
suggests that more information on these very complex substances ia desirable.
To this end National Oancer Institute biochemists have been active in the
identification, synthesis, purification, and analysis of peptides.
Proteins have been subject to intensive study, in view of their
strategic role in living matter, and have been extracted from normal tissues,
from tissues of tmaor-bearing animals, and from tumors themselves. New and
more effective procedures have been developed for distinguishing and
identifying various proteins and enzymes.
Although it cannot be said that cancer is a disease that is inherited,
the probability that an individual may develop cancer is influenced by
heritable traits, dietary factors, and hormonal stimulation. The heritable
traits are a result of the action of the genes found in the cell chromosomes.
The observation that the development of lung tumors in mice is associated
with natural obesity has led to a study of the biological and biochemical
mechanisms by which obesity is produced. A definite linkage between
susceptibility to lung tiinors and a particular gene identified with
obesity has been established, and studies are continuing on the correlation
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totween inherited characteristics and the susceptibility to cancer.
Experiment s are also under way involving the role of filterable
agents, presunalily viruses, in the causation of cancers not previously
associated with viral action.
A study involving nice indicates that the incomplete renoval of
large tunors night extend the life span. This suggests that even partial
renoval of "inoperable tunors" night te of "benefit to sone hur.ian patients*
A good deal of public interest has been nanifested lately in the
subject of the effect of hornones on the body. Much of this stens,
undoubtedly, fron a ntinber of interesting research disclosures. For example,
our own work in this field has produced striking regression in breast cancer
by the application of massive doses of female sex hornone» Similar
injoctions have caused noticeable improvement in prostate cancer patients.
One particular female sex hormone, progesterone, seens potentially
useful in causing shrinkage of advanced breast and prostate cancer, but
was found ineffective when taken orally. The Institute, therefore, is
studying in animal tests a number of compounds rel".ted to progesterone
with a view to finding more effective substances.
The adrenal glands produce hornones which stimulate the growth of
breast cancer, and in advanced cases these glands are renoved surgically.
Animal studies have led to the development of a drUfg known as anphenone,
which inhibits the function of the adrenal glands. Further experiment
nay lead to the possibility of using anphenone to suppress this glandular
function in hunans without resorting to surgery.
An unusual characteristic of ttunors originating in hornone-producing
organs is the excessive production of hornone by the tunor as compared with
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the nornal parent tissue. Many atnornalities result there^by in the "body.
To iuprove the nanagenont of such tuners, our scientists are devoting
considora'ble tine to improving nethods of detecting and measuring these
harmful hormonal effects in the "blood and urine by chcnical and biological
Since castration causes remarkable shrinkage of breast and prostatic
tumors, sttidy is under way of the processes whereby these organs shrink
when deprived of nornal hormonal support by the rem.oval of ovaries and
testes. Present experiments with animals include starvation and special
diets and escposure to heat and cold.
The pituitary gland, located at the base of the 'brain, produces
several hormones that control body growth and the functions of certain other
glands. A nearby organ in the brain is the hypothalamus, which, when
destroyed in animals, affects the pituitary gland and, in turn, the normal
activity of those glands controlled by the pituitary. Those relationships
nay have considerable importance in tumor control. Further investigation
will attempt to define and clarify the manner in which the brain and
pituitary gland cooperate in normal and abnormal growth processes.
Research pharmacologists of the National Cancer Institute are isolating
natural substances and synthesizing new substances which may either induce
or inhibit the growth of cancer. Tests have been developed for determining
the nature and effect of these compounds, their purity, and their lethality.
So far, more than 500 drugs have teen identified as having cancer-destroying
The laboratory scientists have succeeded in creating by synthesis
several typos of new chemical compounds with potency in affecting cancer
in aninals. They have also isolated sone naturally occurring agents from
a considera'ble number of tissues of aninals. Further study on tho nechanisn
of action of tuinor-affecting drugs has been successfully continued.
Close collahoration between laboratory investigators and their
clinical colleagues has been the rule v/ith regard to anir.ial expo rir.ientat ion
with drugs desired by physicians for clinical trial. This situation obtains
particularly in the preparation and adnini strati on of selected drugs to
cancer patients in the Clinical Center.
Other research done by this laboratory will be discussed a little
later under "chemotherapy."
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Field Inve stigations
In the attempt to control cancer with the knowledge at oiir disposal,
the crux of the problem is to shorten the intervals betv/een onset of the
disease and diagnosis, and "between diagnosis and the start of treatment.
Prevention, of course, is of foremost importance as in any disease prohlem,
tVii in fighting cancer the "best weapons are early suspicion, accurate
diagnosis, and effective treatment.
Methods of improving hoth the diagnosis and treatment of cancer
are developed through field demonstration projects, usually in cooperation
with state and local health agencies, and medical and research organizations
and institutions^ One such project has demonstrated the practical useful-
ness of a mass screening procedure which promises to "bring a"bout virtually
complete control of the second most prevalent form of cancer in women.
Next to "breast cancer, women suffer most from cancer of the uterus or
wom"b. The cure rate of uterine cancer if caught in the earliest stages is
95^ - lOC^ as against only 5/o when found in the advanced stages. Unfor-
tunately, 3 O"*!* of k women are first seen and diagnosed in the advanced
In an attempt to develop a test or technique of some kind that would
reveal cancer of the uterus in its earliest manifestations, the National
Cancer Institute undertook two years ago to check thousands of women for
uterine cancer "by means of a cell-examination test. The Memphis-She I'by
County area, in Tennessee, was selected, and what is known as a cytology
screening project was set up, with the cooperation of the local health
department, the covin ty medical society, voliintary agencies, and the medical
school of the University of Tennessee. This test is simple to perform,
is not painful to the patient, requires no expensive equipment. Is accurate,
- 12 -
is inexpensive, and can "be generally applied. The resiilts so far have
Of 165,000 women over 20 years of age living in the Memphis-Shelby
County area, about half have been examined at least onee on a voluntary
basis. Of the first 70,000 about 1,300 - or 2^ - were considered suspi-
cious cases. More than a thousand of these women voluntarily had sections
of tissue taken for microscopic examination, which is the only moans of
confirming a diagnosis of cancer. It turned out that half of these women
had cancer of the uterus in some stage. How many of these malignancies
were unsuspected prior to biopsy? About 60fol Of the women found to have
cervical cancer — called by some authorities "early stage" uterine cancer —
close to 90^ were unsuspected prior to biopsy!
The average age of the women with pre-invasive cervical cancer, when
compared with that of women in the advanced stages of uterine cancer,
suggests that the pre-invasive stage lasts long enough — several years,
that is, — to permit curative treatment if discovered at the yearly checirup.
This cytologic test is simple and easily applied. It will detect
cancer in the early stage of development. Therefore, if the technique is
applied generally on a mass basis, it should be possible to obliterate or
greatly reduce uterine cancer mortality. In view of the fact that uterine
cancer represents the second most prevalent type of cancer in women, it
now appears certain that this project will furnish the datr, necessary to
launch a widespread and Integrated attack on this disease,
I have referred to tissue examination as the only means of confirming
the presence of cancer colls. Pathologists arc the experts and specialis'^s
- 13 -
in this work, and during tho last year they have continued research investi-
gations concerned with the identification and analysis of malignant lesions
in hoth experimental animals and human "beings.
One of the most important recent developments in this field is the
tissue culture technique which uses cellulose sponge as an artificial
medium on which cancer cells may reproduce themselves in a 3-<iimonsional
pattern. This permits the o'bservation of tumor growth and change much as
it appears in the human "body. This new arrangement of tissue growth is now
"being used to test specific therapeutic agents against tumor tissues taken
from the still-living patient, and should provide a more accurate guide to
the clinician in handling cancer cases.
In another kind of project, an atlas on transmissablc malignancies,
giving history, a review of tho literature, detailed morphological descrip-
tions, and photographs, is being prepared "by oiir staff for puhlication under
the auspices of the National Research Council. This should he of great
value in identifying and diagnosing various tumors.
Our pathologists also provide other Institutes of the National
Institutes of Health with such services as the processing and diagnosis of
tissues, analysis of microscopic sections of tumors or suspected lesions,
and autopsies. Much of this work is done for the Clinical Center.
This reference to the new Clinical Center "brings mo to a "brief dis-
cussion of projects, pro'blcms, and plans involving patient treatment.
It is largely in the field of general medicine where the researcher
and the clinician meet to serve the cancer patient. Investigations are
carried on in two major areas - the effects of drugs on cancer, and the
meta"bolic interrelations "between the patient and his tumor.
cov t.zx ar.
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■.3'J'i.a Men SUi,
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■XgOJOi'iCi jj'io ,c!ii
One project has tested the comtincd effect of the two most potent anti-
leukemic compounds known - 6-mercaptopurine and amethopterin. Remissions
were found to occur in about one-third of the patients treated. The study
of acute leukemia will be continued, and an attempt is being made to define
the usefulness of animal Icukemias in predicting what will happen in the
treatment of leukemia in man.
In the coming year a major effort is to be made on the problem of the
chemotherapy of solid tumors. Compounds which have been shown in chemical
pharmacology studies to have significant anti-tumor activity in animals
will be evaluated in clinical trials.
The natural course of a variety of raaligna,nt diseases in terms of the
use and requirement by the patient of nitrogen, minerals, and vitamins has
been carefully observed. Those studies will be expanded to attempt a de-
finition of what it is that the tumor uses and how these materials affect
Since surgery is one of the only two forms of treatment by which cancer
can be cured, this is a field in which improvements and refinements of
technique are continually sought. Our surgeons are investigating the possi-
bilities of treating advanced lung cancer by means of combined surgical and
chemo therapeutic methods. They are also studying special surgical techniques
in an effort to reduce the mortality of advanced cancer of the cervix or
neck of the uterus.
Another project of fundamental importance involves the attempt to
improve the accepted standard surgical methods of treating cancer today. A
review of the causes of failure in many types of cancer amenable to surgical
therapy shows that in a significant number of cases failure occurs because
- 15 -
of wound rocurrenccs. It is believed that these recurrences develop 'bccauRG
cancerous cells lodge themselves along the edge of the incision at the time
of surgery. Search is under way both in man and in animals for means of
reducing or eliminating such recurrence by carefully washing and otherwise
treating wounds with specially prepared chemicals during the postoperative
In addition to specific research, our surgeons serve the patients re-
quiring operative treatment in the Clinical Center, and also furnish our
research people with different kinds of malignant tissues necessary for
microscopic and biochemical analysis.
Research in the field of radiation is particularly important because
radiation both induces and cures cancer. Investigations under way have been
noting the effects of small and large doses of various kinds of radiation on
different kinds of cancers in animals with a view to proper regulation of
dosage to human patients. Different kinds of radiation affect living tissues
differently. Experiments with mice indicate that the biologic effects of
alpha rays from radon arc greater than those from an equivalent dose of
X-ray. It is now well established from experiments with mice and rats that
bone marrow as well as ground-up bone is effective in preventing death in
irradiated animals. Determination of the specific substance which gives
this prptection and how it operates, is the next step.
Studios on the protective mechanism in animals damaged by and recovering
from X-irradiation have indicated that resistance is closely associated with
tho number of one particular type of white blood corpuscle. It was found
that mice with their spleens removed were less resistant to infection than
- 16 ~
intact mice as a result of exposure to sublethal doses of X-irradiation,
Radioactive isotopes have also 110011 studied. One project recently
established the cffectivoncsg of radioiodine therapy in treating metasta-
sizing or spreading thyroid tumors if the primary tumor responds to radio-
active iodine. In another project, through the use of radioactivo-carbon-
labcllod histidine, evidence is accumulating that liver tumor tissue differs
from normal liver tissue in the method of building nucleic acid, which ia
one of the major building blocks of protein.
As a result of recent developments, the Radiation unit plans to expand
its program. Not long ago, a 3 million electron volt Van de Graaff genera-
tor was acctuired as a gift. Two 2 million electron volt machines of the
Bane type were purchased and are being installed. With the further install-
ation of more X-ray therapy equipment, the projects and services of the
branch will be greatly enhanced in terms of typo and number.
Thanks to the special interest in cancer chemotherapy shown by the
Congress, it has been possible to give considerable impetus to research in
this field, and the number of grants awarded to nongovernmental scientists
and Institutions has been substantially increased. The present research
grant program in this area involves about 100 projects amounting to over
Only 25 percent of all cancer cases are diagnosed while the disease is
still sufficiently localized to make possible cure by surgery or irradiation.
As a result of rai^id progress in the search for chemical agents which can
selectively destroy cancer cells and not harm normal tissues and crgans,
there is increased hope for oven those patients who were previously consid-
- 17 -
Ovor 12,000 chemical compounds have 'been analyzed. Approximately 500
tested at the National Cancer Institute have "been found to merit further ox-
porincnt. Although no cures of cancer have "been effected by drugs alone,
chemical compounds have proved iiseful in temporarily checking the course of
the disease and in prolonging the life of many patients suffering from leu-
kemia, Hodgkins disease, cancer of the breast and prostate gland, and some
other forms of cancer
In the managenent of one tj-ijo of leukemia, for example, animal experi-
ments have shown that cancer cells which develop resistance to or dependence
on specific compounds may yet become sensitive to other compounds. This
suggests that when one drug becomes ineffective, treatment may be continued
with another. This chenotherapeutic procedure has been followed with human
patients with good and promising results.
Similarly, with other types of cancer in animals, ten drugs were re-
ported to have brought about permanent euro, especially in mice and rats.
Though there was no transference of effectiveness to human beings with cancer,
these experiments are encouraging, and research in this area is expanding
both intensively and extensively.
To assist scientists engaged in chemotherapy research, a program for
wide exchange of information in this field has been recently established by
the Committee on Chemotherapy of the National Advisory Cancer Council of the
National Cancer Institute in cooperation with the American Cancer Society,
and the Damon Runyon Fund. A variety of activities will be developed
through this program. Included among them will bei formal conferences and
symposia on cancer chemotherapy, the issuance of a periodic compilation of
reports on current research in this field, and the compilation and issuance
of a bibliography of cancer chemotherapy literature covering the period
- 18 -r
19/4-6 through 195^^.
Provision is "being made for individuals and small groups to meet in-
formally in various parts of the country to discuss inter~institutional
studies, standards for evaluating chemical compounds, potentially useful
sutstanccs, and other pertinent au^bjects. One such meeting was held recently
in Washington to discuss methods of screening compounds, and the pharmacolo-
gical and physiological aspects of cancer chemotherapy.
The formally organized Committee on Chemotherapy further plans to tring
to the attention of investigators those chemical agents which may be of inter-
est to them and to assist in obtaining chemicals in sufficient quantity for
Very substantial progress in the search for drugs effective against
cancer is confidently escpocted to result from these coordinated efforts.
Many important research contributions to the problem of cancer are made
by the nongovernmental scientists whose work is supported by grants of funds
representing more than 40 percent of the annual budget of the national
For example, cancer-inducing substances (carcinogens) have been found
in certain industries and in the environment - for example, in automobile
exhaust and air pollutants such as smog - as noted earlier in my remarks.
The search for more of these carcinogens, and the determination of their
extent and danger are being supported by grants.
The role of organic substances such as hormones and enzymes, produced
in the body itself by the normal or abnormal functioning of organs or glands,
is also being stxidied by grantees. These substances may be carcinogenic in
- 19 -
thonselves or may enhance the tunc r-pro due ing properties of carcinogens.
For example, it was discovered that chcnically-induced liver tumors in rats
could be prevented if the pituitary gland was first removed "before the chemi-
cal compound was given to the rat. However, the administration of pituitary
hormones to such a rat would pornit the tur.ior to grow. It must te rcmemtorod
that in all these studies involving experimental animals, especially rats
and mice, similarities with man in terns of "body functions may provide
eventual means of controlling cancer in human beings.
Grant studios of the chemistry of normal and cancerous cells - their
nutritional requirements, the means by which they grow and reproduce, and
the factors that control those activities - are providing the basis for
improved chcmothcrapcutic treatment.
In the field of cancer diagnosis, a new instrument has been developed
for more accuratelj' locating tumors inside the body. The Instrument, called
a somascopo or echograph, makes use of sonar and radar technique to yield a
picture showing the soft tissue in much greater detail than do X-rays,
Work is also going forward on the development of a method for the large-
scale automatic screening of patients for cancer by electrical measurement
of the abnormally bright fluorescence shown by cancer cells under ultra-
violet light. Other studies are being done on various blood tests for cancer.
And of course, new chemo therapeutic compounds are being identified
and tested. This program has been helped considerably by the development of
successful techniques for the growth of various human tumors in rats, guinea
pigs, hamsters, fertilized eggs, and in the test tube.
New surgical skills have boon developed which in combination with better
clinical management of the patient permit the removal of tumors previously
considered inoperable. Excision of various ductless glands has been found to
i^3j-' ■ ,
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arrest temporarily the growth of certain inoperable tumors*
A less expensive type of linear accolorator has "been developed which
can provide nvLLti-nillion-volt radiation. Cobalt 60 is now used as a radia-
tion source for the treatment of cancer.
Grants have ■been awarded for several years to approved professional
schools - nodical, dental, and osteopathic - to coordinate and improve the
teaching of cancer to undergraduate students. A recent study of the interest
in and knowledge of cancer acquired hy these young men and women as a result
of such added materials in the curriculun disclosed a heartening increase in
the students' awareness of cancer and in his acquisition of background in
its diagnosis and treatment. In this manner, the general practitioner in
particular is being more adequately arned.
A gradual and steady increase in the number of scientists trained in the
various fields of cancer research is also essential if this disease is to
bo conquered. As of January 1 of this year, l62 promising young scientists
are being aided by our fellowship program to secure advanced training in
cancer research. In the 16 years of the Institute's pre-doctoral and post-
doctoral fellowship program, some 1,197 young men and women have been
supported in their training to become research scientists. In addition,
since 1938, about 865 youjag physicians have received specialized training,
in such fields as surgery^ medicine, pathology, or radiology in institu-
tions throughout the country in order to improve the care and treatment of
cancer patients in hospitals and clinics
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DISSEMIMTION AND APPLICATION OP KNOWLEDGE
New knowledge of cancer gained through research must be applied to the
prolilem as widely and fully as possible. Close relations are riaintained with
the States through grants to State health agencies in developing cancer con-
trol programs. We are always ready to assist any type of professionally
appropriate group through consultation services.
The prompt exchange of infomation anong scientists is especially in-
portant to the conduct of research. The National Cancer Institute makes a
valuable contribution to this need by publishing a bimonthly journal which
is one of the most important in its field. Exchange of information is also
encouraged through the attendance of our staff members at scientific meet-
ings for the presentation or discussion of papers, and through our coopera-
tion with such organizations as the American Cancer Society and the American
Association for Cancer Research,
In view of the high cure rate for most types of cancer if the disease
is caught in the early stages, an informed and medically cooperative pxiblic
is essential to the successful control of cancer. Therefore, the Institute
is engaged in a comprehensive program of public education in the manifold
aspects of the cancer problem by translating technical medical material into
non- technical language and preparing articles, bronchurcs, and other types
of materials for such groups as nurses and health educators, students, and
for the lay public in general. Such information is necessary and effective
in exploding superstitions, identifying the truths, and securing the inter-
ested cooperation of the average citizen.
In this presentation I have tried to point out briefly the highlights
of the National Cancer Institute's program of activities during 195^» aJ^d
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havG attonpted to project its needs and plans for the coning year, I trust
that ny conncnts have "been helpful in indicating that, no matter how
gradiial or undranatic the progress, progress has hcen made and will continue
to he nade hy the Institute in its research assault upon the nysterios of
cancert As each year passes, more and rioro people are snatched frora death.
Their pain has heon alleviated. More hope, rather than less, is indeed
justified that this dread disease can and will he conquered. I wish to
thank the nenhers of this Cor.inittec for their forhoarance and interest*
I an grateful for this opportunity to appear hofore you to descrihc our
projects, our plans, our hopes, and our needs, and I will welcome any quostiona
you nay have.
Dr. John W. Knutson, Chief Dental Officer
Public Health Service
COMMITTEE ON APPROPRIATIONS
"Dental Health Activities, Public Health Service"
Ml'. Chairman and Members of the Committee:
This appropriation covers activities of the Public Health Service
concerned with the prevention, control, and treatment of dental disease.
The term dental disease embraces a >n.de variety of disorders which affect
more than 90 percent of the American people from early childhood to
advanced age. Included in this group of disorders are dental caries
(tooth decay), periodontal disease (pyorrhea), malocclusion of the teeth
or Jaws, hare lip and cleft palate, and oral cancer.
COST OF DENTAL DISEASE
Health officials have begun only recently to recognize dental
disease as a major national health problem. The dimensions of this
problem are maasured not only in economic terms, but in its effect upon
the well-being of Americans. The cost to consumers in this country is
close to ,1)1.6 billion a year. This means that f}l out of every !Ss6 spent
for personal health services is expended for dental treatment. In
addition, governmental and voluntary agencies spend many millioas of
dollars for this purpose. These expenditures are visible and direct.
Nevertheless, they account for merely a fraction of the total cost of
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Added to these outlays ivS the vast economic burden of lost manpower
to industry, which according to one study amounted to more than h? absences
per 1,000 employees a year for diseases of the teeth and gums. Even data
of this type, however, tend to understate the importance of dental disease
as a cause for industrial absenteeism. Overlooked arc the many disabling
conditions traceable to dental infection. Familiar exainples include
sinusitis of dental origin, iritis associated with infected upper teeth,
impaired hearing arising from malocclusion, and many instances of severe
pain and stiffness of the neck. Nor, in this connection, should we dis-
regard the serious complications which dental infection may cause in persons
suffering from rheumatic heart disease. Even where the condition is not
sufficiently serious to keep a person avray from his job, substantial losses
may occur through impaired efficiency resulting from pain and discomfort.
Moreover, the widespread occurrence of dental disease has serious
implications for the national defense. It will be recalled that in
accwtiulating a military force of some 15^000,000 in World War II, about
50,000 persons were found unfit for service for dental defects - a loss
of approximately three military divisions. ^ comparable and equally pre-
ventable manpower vzastage was again experienced in mobilizing for the
Korean action. A study of 556,000 men rejected or discharged for physical
or mental causes from July 1950 to September 1953 disclosed a total of
more than 17^000 rejections for dental reasons.
We already knox^r that most dental defects can be corrected by modern
dental service. Nevertheless, an intensive program of dental research •>.r<
- 3 -
is needed if we hope to achieve permanent results in combating dental
disorders, '^he logical approach to the public health problem of prevention,
therefore, is through expansion of research.
Research, we feel sure, will ultimately disclose methods not only
for the prevention and control of dental diseases, but also for improved
methods of diagnosing and trsatinf; defects that cannot be prevented. To
this end the National Institute of Dental Research maintains a threefold
program. In research conducted at the Institute, an atteiiipt is made to
broaden our understanding of the biology of dental disease and its
relationships to general health. Through a program of grants, the Institute
stimulates research in dental schools and other institutions, supporting
investigations which could not otherwise be undertaken for lack of funds.
In addition, fellowships are avrarded to assist promising young scientists
to complete their training and to get a start in dental research.
Research Grants ; In the face of mounting costs of research and
increasing needs for scientific personnel, it has become more and more
evident that Federal assistance is required to assure the conduct of basic
studios in the various outsid'-- institutions concerned witli expanding our
knowledge of dental disease. During the past year various research studies
have been conducted in non-federal institutions with the aid of research
grants from the Public Health Service. This vrork has included studies on
- h -
prenatal influonds on tho production of nalformed teeth and .jawsj tissue
culture studies on embryonic dental and on salivary gland tissues; on
heredity as a factor in the causation of dental caries in rats; and on
the effects on the oral tissues of systemic diseases and chronic environ-
In the process of reviewing applications for research grants, our
Dental Research Council is afforded an opportunity to survey the status of
research in dentistry in order to discover neglected areas of research,
and to encourage the interest and c;fforts of competent workers in these
fields, '^ho modest increases in funds made available for ros.-sarch grants
last year enabled us to extend support to several previously neglected
areas of research, particularly in the fields of unzymology, genetics,
growth and development, and periodontal disease.
Research Fellowships : A recent survey by ttie American Dental
Association of needs in dental education pointed to the shortage of
trained research workers and teachers. The pre- and post-doctoral
fellowship program of the Institute assists in the solution of this
problem. Research fellowships are awarded to encourage promising
students to continue their training in preparation for careers in teaching
or raR-.;arch, The increase in funds made available for this program
during FY 19'^$ ^^Jill undoubtedly yield results. These funds have also
permitted the inauguration on a sinall scale of a program designed to
interest undergraduate students in a research career.
Laboratory and field research : Our studies in dental caries are
being continued in the fields of bacteriology, histopathology, and bio-
chemistry. Although water fluoridation has given us an effective tool
for handling part of the problem, we still have much to accomplish for
our adult and rural populations. An approach of considerable promise in
the control of caries for these people is through the use of antibiotics
or chemotherapeutic agents. An intensive search for an effective agent,
free from such side-effects as sensitizing reactions, is in progress.
The virtue of antibiotic control lies in its applicability to all age
groups, as well as its ability to exercise an immediate protective action
on the tooth.
These studies are already sufficiently advanced to suggest a
promising area for investigation - experimentation with germ- free animals,
Since cariesdoesnot occur in a germ-free environment, the germ-free
animal will give the investigator a new means of measuring the activity
of individual types of bacteria in producing caries xjhen introduced to
the oral cavity.
Studies of tooth structure by optical and electron microscopy are
revealing the nature of the caries process, bringing to light the path-
ways by Tjhich bacteria invade tooth substance, and the manner in which
the organic and mineral components are destroyed.
Significant advances are being made in research on the chemistry
of tooth structure. The resulting knowledge of variations in chemical
composition and properties can subsequently be related to individual
differences in caries susceptibility.
Fluoridation of public water supplies as a dental public health
measure will be reported on in some detail latero As with all programs
that progress from laboratory - to field trial - to application, there
remain important areas for investigation which must be continued if
maximum values are to be derived from major research advances in any
given fielde Current research at the National Institute of Dental Re-
search relating to fluoridation is designed to explain how fluorides
prevent decay and to increase our knowledge regarding the metabolism of
Periodontal disease, the major cause of tooth loss in adults,
affects 3 out of 10 of our 30-year-olds, Among the older age groups the
ravages of pyorrhea are even more prevalent, for as many as 85 percent
ultimately suffer from this dental maladyp Since elderly persons are a
large and increasing proportion of our population, it is clear that
periodontal disease vdll assume even greater significance in the futureo
The need is therefore urgent to enlarge our efforts to determine the
basic etiologic factors of this disorder.
Studies on periodontal disease have already suggested that in-
fection is subsequent to a noninfective factor, concerning which little
is known. Progress is being made in the development of fundamental
knowledge of normal soft tissues of the mouth and of the structural
alterations associated with other diseases.
Steps are being taken to fill the gaps in our knowledge of the
epidemiologic characteristics of periodontal disorders. Among our
noteworthy recent accomplishitients is the foriTiUlation cf a method for
measuring the occurrence of pyorrhea in large population groups o Much
knowledge can be gained by observations in a community to discover how
many people are affected, what types of the disorder are involved,
and at which age its earliest manifestations are noted. The epidemiologic
approach, which has been employed so effectively in research on caries.,
should yield definitive information on the factors associated with the
occurrence of periodontal disease©
Clinical research; Establishment of the Clinical Center has
provided an opportunity to bring together the laboratory and the
clinical scientist. In addition, it has encouraged an interdisciplinary
approach to research, which is being brought to bear productively in
our studies of wound healing, of leukoplakia (a precancerous condition),
and of periodontal disturbances « One project of interest centers on
methods of simplifying the treatment of malocclusion. This is a con-
dition in which the teeth are either improperly arranged in the jaws,
or in which the relationships of the teeth or jaws. are structurally or
functionally out of balance. Malocclusion often causes serious disfigure-
ment and loss of function, creating problems in individual adjustment and
even leading to emotional disturbances. Progress tovTard simplified therapy
offers a hope of widening the availability of treatment to the 1 out of
every 10 children X'jhose occlusal irregularities are severe enough to
require orthodontic care. Another project in the growth and development
field seeks to establish a sound basis for the treatment of cleft palate
and hare lip, congenital defects foiond to occur once in every 800
live births. Our cleft palate project is concerned •(^rith investigating
the role of muscle forces in restoring functional anatomical relation-
ships, and with the effectiveness of speech therapy and other treatment
in mitigating psychic injury through early correction of the deformityo
The broadened attack on periodontal disease will receive par-
ticuiftr emphasis at the Clinical Center, A method for assessing the
severity of periodontal disorders has already been subjected to clinical
trial o It is now being used in a study to determine the systemic
derangements, such as diabetes and rheumatic heart disease, associated
with diseases of the tooth-supporting tissues. This approach is being
facilitated by the ready access of the unusually complete clinical
records maintained at the Center and the diversity of diagnostic tests
performed for each patient.
For the immediate future, data are to be accumulated on the use
of general anesthesia in oral surgery in order to establish a base for
evaluating new, rapidly acting drugs for dental use. The Center answers
our long-felt need for a means of validating clinically promising leads
from the laboratory.
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PREVEMTION A.ND CQtlTRQL OF DENTAL DISEASE
As I have indicated, t?ie Public Health Service is deeply committed
to the search for new knowledge regarding the cause and treatment of
dental disease. A corollarj'' concern is in developing effective
preventive techniques and expediting their application.
Water fluoridation ; The fluoridation of public water supplies,
developed after long and painstaking investigation of its safety and
health-giving values, has been endorsed in principle by all the major
health organizations of the Nation. It has been definitely shown that
fluoridated water can reduce caries by as much a s two-thirds. Demon-
stration that this method of caries control is possible over a lifetime
at an expenditure of $7 per person is the most outstanding achievement
of dental research to date. Despite the promise inherent in this
measure, progress in gaining community acceptance of water fluoridation
has been slow. At the present time rnly 1,0U0 cities and towns, with
an aggregate population of 20, It million have adopted the procedure.
This situation reflects in part the lag between discovery of knowledge
and its translation into action. The necessary knowledge regarding
the benefits and safety of fluoridation has been at hand for some time
novT, It remains only to have this knowledge put to work as rapidly
and effectively as possible.
Work is being continued in order to simplify and refine current
fluoridation procedures, as well as to test the suitability of various
fluoride compounds. Progress is also being made in determining the
relationship between climatic conditions and the optimum fluoride
concentration. It has been shown, for example, that in warm climates
- 10 -
fairly lower concentrations afford optimum protection.
Direct application of fluorides ; At the present time, topical
application of fluorides is the only established method f or control of
caries among rural populations lacking central water supplies. The
most effective fluoride solution and concentration, the optimum number
of applications, and the simplest method of administerinf^ the applica-
tions are problems receiving careful investigation.
Defluoridation studies ; In more than 600 communities, the
water supplies contain amounts of naturally occurring fluoride
sufficient to mottle tooth enamel. Appreciable gains have been made
in solving the problem of how best to remove excess fluorides without
losing the beneficial effects of an optimum concentration. In studies
under way at Bartlett, Texas, and Britton, South Dakota, bone char and
activated alumina show much promise as media for reducing fluoride
DENTAL Rn; SOURCES
The supply and availability of dental personnel have a direct
bearing upon the Nation's dental health. The most effective use of
these resources, coupled with a vigorous approach to expansion in the
years ahead, are issues of singular importance. Until preventive
dentistry has had years of nationwide application, the large share
of our control efforts will remain a responsibility of the private
dentist treating the individual patient. The Public Health Service
therefore works closely with health organizations, providing important
advisory and technical services. These activities are directed toward
maximizing the use of existing resources in personnel and facilities.
- 11 -
and toward continuing study of the factors necessary for expansion and
off active utilization of these resources.
Manpower shortar;cs ;-- Available evidence indicates a shortage
of dentists which is aggravated by their uneven distribution. Dental
schools are currently accomodating capacity enrollments^ producing
graduates in excess of the number of dentists who die or retire each
The growth of population^ however, is outstripping the rate of
increase of dentists. Should those trends continue, the ratio of
dentists to population will continue to decline. In order to insure
orderly planning and development of programs for training of the number
of dentists and auxiliary workers needed, the Public Health Service
is collaborating v/ith outsido organizations on studies of the problem.
Information is now being assembled on the dentist supply of States
and counties which may be of extreme value in connection with estimates
of resources i or civil defense and public health activities. A related
area analysis nearing completion will provide previously unavailable
material on the supply, professional service expectancy, and patterns
of withdrawal from the labor force of dental hygienists.
Since the number of graduates lies at the heart of the problem of in-
creasing manpower, some of our studies are concerned with educational costs,
unmet needs for construction and equipment, and strategic location of
new schools. Of considerable interest to school financing is a report
on the costs to the student of obtainihg a dental education, which will
be released during the current year«
Manpower utilization ^ ■ Particular interest and attention in
r'icont ycarc have i'ocuGod upon mothodE of extending the rorvice capacity
of our pi'Gsont supply of denti::^t3. Much of the interest stems from
findings of our studies, which suggested that most dentists can double
their output through a more effective use of qualified auxiliary pijrsonnel
and a more efficient arrangement of equipment. To encourage the widest
possible use of these labor-saving rae-S;.hods, demonstrations in this area
will be continued.
¥e are also moving forward in our observations on methods of
practice and of financing dental care that may increase the effective
use of manpower and the volume of dental services. A study completed
during the past year has made available information on the time and
service requirements involved in meeting the continuing needs of a
group for comprehensive dental care. The findings of t'lis study offer
valuable insights into the naturo and problems of prepaid dental care.
Our studies in this field will bo broadened to include actuarial^ opera-
tional, and organizational problems of dental prepayment plans.
As in other fields of concern with the Nation's health, the
Public ;Health Service has direct as well as indirect responsibilities.
In field studies and in intramural research, the Service assesses
health needs, develops new methods of control, and conducts demonstration
projects. These are direct responsibilities. A second role is illustrated
by the stimulus and financial support given to research in other institu-
tions and agencies. Moreover, States and localities call upon the Service
for advice and consultation in meeting the day-to-day problems of
applying existing knowledge of public health practice. This method of
approach, applied only recently to dental health, has already proved its
Dr. James Watt
Director, National Heart Institutii
Public Health Service
COMMITTEE ON APPROPRIATIONS
"Salaries, Expfenses, and Grants, Nattptiel H'='?-rt Institute''
( HISTORICAL BACKGROUND )
('The budget proposal for Fiscal Year 1956 of the
National Heart Institute is based upon the current status of
the several aspects of the Institute's general function,
established by the Congress, of supporting and conducting
research and training in diseases of the heart and circulation
and of aiding the States in the development of community
programs for the ::ontroI c£ those diseases.
( Since the National Heart Institute came into being in
1948, it has through the operations made possible by the
annual Congressional appropriations! developed into a major
influence in the nationwide effort against heart disease that
is making steady and highly encouraging progress on many
( The National Heart Institute program for Fiscal Year
1956 is designed to take advantage of the opportunities for
research and its application that are possible today only
because of the gains of the past several years. The program
is oriented toward -che gathering of knowledge and its use
against congenital heart disease, rheumatic fever and rheumatic
lieart disease, high blood pressure, and hardening of the
arteries--the major killers and cripplers of the heart and
circulatory system. )
Mr. Chairman and Members of the Committee:
THE IMPORTANCE OF THE HEMT DISEASE PROBLEM
In the changing national health problem of recent years which
has seen the chronic diseases come, to the forefront, heart disease--
lar^e and complex group of ailments of the heart and blood vessels
--has played a major role. Twenty years ago, less than a third of all
deaths were attributable to heart disease--420 000 out of 1 342 ,000
in 1933. Today cardiovascular disease causes more than half of all
- 2 -
deaths in the United States--an estimated 730,000 out of 1,470 000
Although the major bulk of deaths from heart disease is
among older persons^ it is far from being a problem only of the aged.
In 1953 for example of all persons dying from heart disease almost
a third (31 percent) died at ages under 55.
During the past three decades the risk of dying from heart
(1) has decreased for ages ur>der forty-five;
(2) has shown little change in the important age group 45
to 64 for males and females combined;
(3) has gone down for females 45 to 64;
(4) but has gone u£ considerably for males 45 to 64.
The significance to the nation's defense, manpower and economy
of this most important trend is suriined up in the stark fact that
Half of all the white males who die in their forties and fifties now
die of the various form? of heart disease .
While good data on the prevalence--the amount--Q£ heart disease
are not available, it seems reasonable to estimate that there are
not less than 10,000 000 persons in the United States suffering from
some form of heart disease. For every death from heart disease, there
are probably many more sufferers alive either severely crippled or
restricted or certainly not as effective citizens and community
members as they would otherwise be.
These facts highlight the importance of the problem of heart
disease and emphasize the importance of the objective of the National
Heart Institute program: the reduction of untimely death and dis-
ability from heart disease and the consequent bringing of added years
of healthy, productive, and happy living to more and more people.
That this is a realistic and attainable goal is shown by the
state of today's knowledge about heart disease in which already
- 3 -
some types can be prevented and some cured; in which it has been
shown that many kinds of heart diGease--either without therapy or
by medical and surgical treatment, including some formerly considered
incurable or rapidly fatal, can be reversible ; and in which most
patients with heart disease can be materially improved by proper
treatment and management. The programs of the National Heart
Institute have played important roles in bringing about this progress,
HEART RESEARCH GRANTS
The stimulation given by the research grant program of the Heart
Institute has significantly increased the productivity of cardiovascu-
lar research. The studies carried out represent research progress
that would otherwise not be made, since all projects supported are
in addition to those undertaken by the institutions with their own
funds. The program does not supplant support from foundations,
private, philanthropic, or voluntary health organizations, but has
encouraged continued and increased support by such groups.
More than 629 research projects currently under way in over
100 universities and hospitals in all parts of the country are
receiving support through the grant urogram. These projects encompass
investigations in both basic and clinical areas related to heart
disease, with concentration upon major problems such as hardening
of the arteries and high blood pressure. Following are a few of the
many achievements resulting from the research grant program.
Arteriosclerosis : Scientists at the Michael Reese Hospital in
Chicago have continued investigations related to the sex differences
in the incidence of coronairy arteriosclerosis. They have found that
the administration of cholesterol to sexually mature female chickens
does not produce coronary arteriosclerosis, although the chickens
- 4 -
of the same age. The administration of female sex hormones to male
chickens prevented or reduced the incidence of coronary arterio-
sclerosis. The female sex hormone, therefore, has been shown to
exert possibly a protective effect against the deposition of
cholesterol in the walls of the coronary arteries.
Another investigator, at the Mount Zion Hospital in San
Francisco, is establishing the important part played by cells of the
liver in removing dietary-derived cholesterol from the blood. This
indicates that abnormal functioning of these cells may be an important
factor in the production of high blocd cholesterol levels following
high cholesterol dietary intake. This study contributes information
regarding one of the fundamental mechanisms for the control of the
cholesterol level of the blood.
It is recognized that atherosclerosis can occur in man without
apparent prior elevations of blood cholesterol or lipoprotein levels.
Several workers, therefore, are investigating the artery wall itself
and its relationship to the formation of the lesion. At the Southwest
Foundation for Research and Education, data are being accumulated
demonstrating that the aorta (the main blood vessel from the heart)
is capable of manufacturing cholesterol and lipoproteins. These
studies are continuing in an attempt to determine what factors
influence the rate and distributior. of this process.
The incidence of arteriosclerosis among young people, as well as
those with advanced age, is continuing to be investigated. The effect
of diet and environment among people of different genetic background
is being studied by researchers of Boston and the University of
Minnesota. A scientist at Lousiana State University has developed
a new staining technique, which he is utilizing in studies on the
incidence of arteriosclerosis among young persons in this country
- 5 -
and abroad .
Hypertension ; Fundamental research on the mechanisms of blood
pressure control continues to be productive. Investigators at the
Cleveland Clinic have shot/m that plasma from persons with hypertension
is constrictive to normal blood veasels. The vaso-constrictor material
responsible, serotonin, has been isolated, crystallized, and structure
determined. It is now being tested to learn its normal function in
the body and its possibili;:ies as a contributing factor to the clinical
entity recognized as hypertension.
Disturbances in the balance of body constituents known as
electrolytes (salts) appear related to the mechanism of high blood
pressure, Clearer definition of the relationship of these electrolytes
to one another and to the mechanism for the control of blood pressure
is undergoing investigation at the University of Pennsylvania. At
Georgetown University, an investigator is studying the effect of drugs
which appear effective in reducing high blood pressure. He has
recently reported clinical findings or. a new substance, pentapyrro-
lidinium (Ansolysen) which appears to be more potent than any drug
Continuing investigation of the possible part that the kidney,
the endocrine glands, and the nervous system play in hypertension is
producing leads that more clearly define the delicate balance of body
blood pressure control. Only through such research dedicated to the
better understanding of these fundamental mechanisms can the problem
of high blood pressure be eventually solved.
Rheumatic Fever : The first phase of a cooperative study on the
effect of drugs used in the treatment of rheumatic fever has been
completed. The second phase, a long-term follow-up of patients on
whom these drugs have been used, is underway. Investigations of this
- 6 -
type are of importance in demonstrating the effectiveness of therapy
against the chronic invalidism induced by rheumatic fever. Community
studies on the prophylactic use of sulfonamides and penicillin for
patients having suffered an attack of rheumatic fever indicate that
the incidence of subsequent attacks can be markedly reduced in
populations where these drugs are used prophylactically.
Aside from the clinical findings indicating the presence of
rheumatic fever, the need for objective tests of rheumatic activity
has long been recognized Studies at Irvington House, New York, and
others, have demonstrated that C-reactive-protein, a material produced
by tissues in response to inflammation, is an extremely sensitive and
reliable laboratory test for the detection of rheumatic activity and
as a guide to the treatment and management of patients with rheumatic
Surgery : An important new method which enables the cardiac
surgeon to perform operations within the heart has been developed at
the University of Minnesota. Blood returning to the patient's heart
is channeled to a donor, circulated through the donor's body where
it is oxygenated, and then returned to the patient's circulation
beyond the heart. The heart thus remains relatively free of blood,
and those anatomical defects which previously seriously interfered
with the patient's activity and life span can be repaired. This
technique permits the surgeon to work within the heart for longer
periods of time than is possible with other techniques.
Hypothermia, reduction of body temperature, has passed the
first experimental stages and is now being used to permit operations
on the interior of the heart, particularly where the valve leaflets
of the heart have become adherent. Modification of techniques
developed at Hahnemann Medical College, Philadelphia, are now being
utilized in clinics throughout the country. Follow-up of patients
- 7 -
undergoing operations utilizing these techniques indicate that persons
whose careers have been interrupted by this disease process are now
again active members of their corrmunity.
It has been observed that the heart and vascular system of
the pig is remarkably similar to that of humans. This animal,
however, because of its size, has not been suited to laboratory
experimentation. A pig small enough to be relatively easy to keep
in the laboratory throughout its entire life span is being developed
genetically at the University of Minnesota. This animal, with a
mature weight of about 60 pounds, is now being used in studies in-
volving repair of cardiac and blood vessel abnormalities as well as
in diseases caused by viruses affecting these organs.
R ehabilitation : The field of rehabilitation is hampered by a
lack of solid and fundamental scientific information about human
performance. The need for the application of the concepts of the
methods of the physical and functional sciences to this problem has
long recognized. A research project studying the factors underlying
human performance has been initiated whereby the methods of several
scientific disciplines are being cooperatively focused upon this
problem. It is anticipated that projects of this type will supply
the basic material leading to a clearer understanding of ways to
rehabilitate the patient recovering from cardiovascular disease.
RESEARCH AND CLINICAL TRAINING
Research relating to the cause, prevention, diagnosis, and
treatment of diseases of the heart and circulation is producing
results which are reducing the disability caused by this group of
diseases. Continued production of effective results depends upon
the introduction of new skills and trained personnel in both the
areas of cardiovascular research and of clinical application of
- 8 -
medical knowledge. The Institute's programs are helping to meet
Research Fellowships : This program, by offering encouragement
and financial assistance to qualified individuals to enter upon a
research career in the heart disease field, aids in relieving the
scarcity of trained investigators. The need for capable researchers
is a continuing one, since skilled workers, able in the conception,
administration, and execution of high-caliber studies are few in
number in comparison to the oppor ;.unitie3 for important research. On
this activity depends the future core of trained investigators for the
attack on theamultitude of problems existing in the cardiovascular
Training Grants : Teaching grants make it possible for schools
of Medicine, Public Health and Osteopathy to continue to coordinate
and improve the teaching of cardiovascular disease subjects to
students. The need for improvement and expansion has been recognized
by the schools and the funds made available are utilized by them to
fulfill the needs of this objective within their local situation.
Much has been done toward this end individually, and mutually^
through meetings of the cardiovascular Teaching Grant Program
Directors from each institution. • The need, however j continues to
be a growing one, for as research discoveries are made new methods
of instruction must be developed to include them, in Order that
graduating students may enter their professional careers equipped
with the most advanced knowledge.
The program also includes training stipend awards to young
physicians for special training in heart disease diagnosis and
treatmsHt. This is an essential investment in helping to provide
the medical care needed by the people of this country. The preseiit
number of physicians and related medical personnel skilled in cardio-
vascular techniques, specialized procedures, and methods, is
seriously inadequate compared with the amount of heart
and blood vessel disorders in the natiori. Tratiri,-si'g at-f.piajl^-e •
are providing a means fot partially overcoming this shortage. The
development of special skills necessary for patient care is important
to provide for the still increasing nuvnber of persons ^o will 50 to
their physicians for help because of heart disease,
NHI DIRECT RESEARCH
The Heart Institute's program of direct research is aimed at
the improvement of the prevention and treatment of diseases of the
heart and blood vessels, This aim is served by 1) the development
of fundamental information concerning the heart and circulatory
system and 2) the correlation of such information with existing
knowledge and new information acquired in other centers of research
and its application to the treatment of heart disease. These studies
are conducted on a broad front, utilizing the skills of many disci-
plines, in order to further knowledge of fundamental biochemical
and physiologic processes and at the same time to develop the
■ipplication of such knowlsdge to the treatment of the cardiac patient.
The accomplishments of the past year represent in large part
che further development of projects instituted in earlier years. New
ievelopments in many of these have directed efforts along new channels
and certain new projects holding considerable promise for the future
have been undertaken.
Progress in Arteriosclerosis Studies
Atherosclerosis or hardening of the arteries is the basic causo.
of much of the illness and death from cardiovascular disease. When
located in the coronary arterie? which supply blocd to the be.-rr
muscle, it may lead to sudden death, to repeated coronary heart
attacks or to progressive heart muscle damage and congestive heart
failure, in the large vessels of the extremities it may lead to
- 10 -
stoppage of blood flow and the development of gangrene. When athero-
sclerotic lesions are located in the vessels of the brain they may
lead to the damage to specific brain regions commonly known as stroke.
Once thought an inevitable part of the process of growing old,
it is now established that atherosclerosis is ^^eflnitely a disease
which afflicts some at a relatively early age, others practically
not at all. It has further bean established that atherosclerosis
is associated with certain abnormalities of the handling of fatty
substances in the body either as a result of defective body mechaniSiaF
or abnormal fat intake. As a result, deposition of fatty materials
occurs in the artery walla, initiating the atherosclerotic process.
Intensive studies of the mechanism by which fatty substances
are carried in the blood and disposed of by the tissues have been
under way in the Heart Institute laboratories for some time. These
hold the best promise of eventually revealing the nature of the
fundamental abnormality leading to atherosclerosis and pointing a
way to its prevention and treatment.
Fatty materials differ from most other body constituents in
that they do not dissolve to any appreciable extent in water. Hence
they must be carried in the blood stream attached to other materials
which keep them in solution. The nucleus for the transport of fat in
the blood is provided by certain of the plasma proteins. Upon these
may bo heaped layer upon layer of fatty materials until the individual
particle may actually reach microscopically visible size.
A "clearing factor" system whose components have been described
by Heart Institute scientists acts to strip the fat from these
aggregates converting them to smaller more stable, and less dangerous
entities. It has been shown in the last year that this clearing
system has its primary function In the tissues, presumably making
- 11 -
fat available to the cells for their use. Further study of the
tissue handling of fat may reveal the defect which, in atherosclerosis,
permits the dangerous accumulation of these fatty aggregates in the
Attention is also being devoted to the proteins upon which
these fatty substances are carried to determine whether the abnormality
in atherosclerosis may sometimes be in the nucleus of the particles.
The proteins are being labelled with radioactive tracers to determine
whether the protein is the same in the small, normal, harmless fat-
proteins (lipoproteins) as in the larger ones associated with the
development of atherosclerosis. Meanwhile studies of patients are
continuing to further define some of the abnormalities associated
with the development of atherosclerosis and the effects of a number
of drugs and hormones on fat-handling in these patients.
A new technique for the separation of the various fat-bearing
proteins of the blood has been developed which has two great ad-
vantages over previous methods: 1) it eliminates the most expensive
instrument formerly required for such studies and should make possible
research on blood fats in many places where the expense had previously
discouraged it; and 2) it makes available for chemical analysis
special lipoprotein fractions which could previously not be analyzed
individually; abnormalities in composition as well as amount of these
fat-protein complexes have already been detected in individuals
Research in Hypertension
Efforts in the field of hypertension (high blood pressure)
have been concentrated chiefly on the search for a drug which can
be used safely and on a long-term basis to keep the blood pressure
at normal levels in individuals with hypertension. There is good
- 12 -
reason to bslieve that such a drug would be effective in preventing ^
or reversing the deleterious effects of this disorder.
The first drug with blood pressure-lowering effects isolated
in Heart Institute laboratories has been carried through to trial
in patients in the Clinical Center, The evaluation of this drug,
andromedo toxin, a substance isolated from Rhododendron leaves, is
now nearing completion. While the drug may find a place in the
short-term treatment of certain types of disorder associated with
acute elevation of the blood pressure (such, possibly, as the
eclampsia of pregnancy), it seems unlikely that it will be useful
for the treatment of hypertension generally. This is so because
its effect is rather short-lived after each dose, because it is
effective only by injection, and because undesirable effects are
detected in patients with doses very close to those required to
lower blood pressure. The latter finding is illustrative of the
importance of early testing in man in the process of drug development,
since the subjective toxic effects noted in man cannot be detected
in animals. It is in such research that the Clinical Center proves
extremely valuable since this facility is ideally suited for
carrying out drug studies which include early human testing.
Although experience with andromedotoxin has been somewhat
disappointing, a number of other agents, both synthetic and naturally-
occurring (isolated from plants) , are under study and include several
promising leads. It must be borne in mind that the development of a
single new drug useful and dependable for the treatment of human
hypertension would repay many times over the time, effort and money
expended on such a project.
- 13 -
Advances in Congestive Heart Failure
The symptom complex known as heart failure may occur as a
result of any of the major diseases of the heart. The familiar
picture of breathlessness , of swelling of the ankles and legs, is
attributable to failure of the heart to be able to carry its work
load and to the abnormal retention of salt and water by the kl^lney
which results. The problems of cardiac failure are being attacked
in several ways.
A substance in normal blood was shown by a Heart Institute
investigator to exert an effect on the heart beat similar to that
produced by digitalis, the drug long universally recognized as
highly beneficial in the treatment of heart failure. It was thought
that this material might be a hormone and involved in the regulation
of the contraction of the heart muscle. Using large amounts of
.: . liver as a starting material and monitoring each step by determining
the effect on heart contraction, minute amounts of this substance
. have now been isolated and some of its characteristics determined. • ;..
While its source within the body has not yet been identified and
its function in the control of the heart beat is not yet determined,
the isolation procedures which have been worked out prepare the way
for the preparation of larger amounts sufficient for its chemical
identification and for studies of its role in the normal and diseased
It has previously been shown by Heart Institute investigators
that the abnormal retention of salt and water which occurs in ex-
perimental heart failure is dependent upon increased secretion of
salt-retention hormones by the adrenal glands, these hormones in
turn exerting their effect upon 'the kidney. An improved method of
assaying for these salt-retention hormones has been' developed ;ivu1.
- 14 -
applied to the study of patients with heart failure. Increased
amounts of aalt-retentlon hormone have been demonstrated ir. the
urine in disorders associated wj.th fluid retention. Studies are
in progress to determine the normal stimulus which causes the
adrenal to secrete these hormones so that the nature of the abnormal
stimulus in heart failure can be evaluated,
The demonstration of the involvement of adrenal hormones in
the salt retention of cardiac failure along with the need for a
drug which can be used to control the retention of salt in cardiac
patients when taken by mouth has stimulated a new program to discover
an antagonist to the salt-retention hormones - that is, a compound
of generally similar structure, so modified as to prevent the action
of salt-retention hormones and reverse their effects. A large
number of new synthetic steroid hormones withTaarious structural
modifications are available from the drug industry as a result of
their interest in such substances for the treatment of arthritis.
Arangements have been made to draw on this source of potentially-
useful drugs and a procedure has been worked out which promises to
'■.be the first useful test for such activity in animals.
D rug Investigations
In the area of the development of therapeutic agents progress
has been made in several fields. A fundamental discovery deals with
the mechanism by which drugs are converted in the body to inactive
products. The latter is the process by which the body disposes of
'., most medicinal substances and the speed at which such disposal
progresses limits the usefulness of many drugs because of either
too long or too short a persistence in the body. It has been found
that a wide variety of chemical conversions is carried out by a
small number of similar and closely related enzyme systems. These
- 15 -
enzyme systems are fco be found in little-studied submicroscopic
particles in the liver and the enzymes exhibit an extraordinary
degree of non-specificity,, The importance of an understanding of
these mechanisms in the design of drugs for specific actions in the
body is obvious. It may also be predicted that a finding of such
fundamental importance will have implications and applications which
are not yet foreseen.
The studies of the anti- inflammatory drug phenylbutazone
referred to in earlier reports have led to further research with
related compounds utilizing information gained from the study of
the route of breakdown of phenylbutazone in the body. Several in
this series show promise in preliminary trial*, yielding the anti-
inflammatory effects of the parent compound without producing the
abnormal retention of salt ana water which limits the usefulness
.. A search for improved drugs for the treatpient of abnormal
heart rhythms has been Intjtttuti^ and a potentially useful group of
compounds has been uncovered and is uader study. One has been
discarded, after trial in patients, since it represents no improvement
over procaine amide, an agent whose usefulness was first demonstrated
in Heart Institute laboratories. Other anti-arrhythmic drugs should
be ready for trial in patients in the near future.
New Surgical Techniques
In the field of heart surgery, advances have been made in
the improvement of diagnostic methods. A technique for measuring
pressures in and obtaining blood samples from the left side of the
heart has been developed. This makes this portion of the circulacion
accessible for the first time and makes possible improved identifica-
tion of abnormalities of the valves and chambers of the left heart
and.facilitates ' the diagnosis of abnormal communications of the
left and right side of the heart. • . ■ •
Several projects in the field of hypothermia have yielded ■
significant progress in the last year. Hypothermia, a marked
reduction of body temperature sometimes referred to as artificial
hibernation, markedly reduces the metabolism of body cells and
hence their requirements for oxygen. The circulation can therefore
be interrupted or drastically reduced for longer periods than are
possible at normal body temperature without causing irreversible
damage due to oxygen lack. This can be of great value in the
repair of certain defects of the heart, since operations can be
performed under direct vieion. in a bloodless field.
The usefulness of the hypothermia in cardiac surgery has been
limited,, however, by the occurrence of serious abnormalitlea of heart
rhythm. A method of preventing these abnormal rhythms by blocking;
certain nerves supplying the heart has been devised and successfully
applied in dogs. After additional experience has been gained in .
animals, this promising technique should be applicable to human
; • APPLYING KNOWLEDGE ABOUT HEART DISEASE
One of the major objectives of the National Heart Institute
program is to assist communities in the application of what is already
known to reduce death, disability, and suffering caused by heart
disease. Grants-in-aid to States and Territories are made according
to n formula based on the population and economic needs of the States
for the purpose of encouraging and promoting the mechanisms by which
community heart programs can be facilitated.
These grants-in-aid are materially assisting the States in the
development, improvement, and extension of their total programs. Their
diagnostic clinic services are being extended and improved through
- 17 -
such things as training courses for clinic personnel, the addition
of social ^nursing^and nutrition services, and the acquisition of
new and improved diagnostic equipment. Their professional educa-
tional programs by the use of seminars, work shops, publications,
and so forth have extended the nevjer knowledge and techniques to
the practicing physician to help him maintain a high level of
competency in the care of his patients.
States have increased the scope of their rheumatic fever
programs to include preventive measures in addition to diagnostic
and follow-up services, and to intensify casefinding efforts.
Assistance is also given to States in technical matters in the
development; improvement and extension of community programs for
heart disease control.
For example, the Service is aiding in the establishment of
nuclei training centers to provide nurses in practice an opportunity
to gain knowledge for the prevention, care, treatment and rehabili-
tation in cardiovascular disease.
Improved methods of case management can be of help to cardiac
patients only if they are known and used by the physicians of the
community. Here the technical assistance program is helping to
extend the knowledge of new techniques through professional education.
A series of tape recordings, covisitmting a course in heart sounds
as a valuable aid in diagnosis of heart disease, were developed
and distributed through the public Health Service regional offices
.. to assist physicians in recogr.izing heart diseases in their patients.
Other efforts in professional education are the dissemination
of information which will be useful to the treatment of patients
such as the statement on prevention of rheumatic fever being jointly
sponsored by the Public Health Service and the American Heart
- 18 -
Association; preparation of exhibits for medical meetings, and
the preparation and dissemination of booklets such as the Low
Sodium Meal Planning Booklet which is helpful to physicians for
use with patients.
The development of better techniques in the control of
cardiovascular diseases and the evaluation of the present methods
are also important functions of technical assistance to States.
The gap between the discovery of new knowledge in laboratories,
clinics and hospitals, and the final use of this information in
assisting communities in solving some of their problems in heart
disease, can be narrowed considerably by community research
programs designed to test, oil an experimental basis and with proper
evaluation, many of the newer developments so that considerations
can be made as to which of these developments can be adapted to
their heart program. This operational research area of activity
provides for the development and evaluation of methods and techniques
for the practical application of clinical research findings; in
addition, it provides for investigation of some of the public health
aspects of heart disease.
PREVENTING RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE
Particularly illustrative of the opportunities that evolve
from rescarch--for the application on a wide and intensive scale of
knowledge--is the area of prevention of rheumatic fever and rheumatic
heart disease. As indicated in previous statements, the state of
knowledge today is such that there is a sound basis for a strong
preventive program, with the. physician the keyatonc and with
official and voluntary health agencies working together.
Many thousands of new cases of rheumatic fever still occur
each year, although the disease has been dcclining--a.t least in
- 19 -
numbers of deaths--for some time. The new cases that occur, add
to a prevalence of unknown but probably large proportions. And
mortality, moreover, continues to be far higher than it should be:
some 15C0 children and young people under age 25 died of rheumatic
fever and rheumatic heart disease in 1953; over 19,000 others above
age 25 also died from these causes.
The opportunity for prevention of rheumatic fever through
public health programs developed by communities in accordance with
local needs is becoming better known. A great deal is being done
in a fair number of communities and States in this regard. Much
of this effort is a result of a cooperative endeavor betwaen the
American Heart Association and the Public Health Service which was
initiated in January, 1953, with the icsuanse of a statement on the
prevention of rheumatic fever. Given wide diaaemination, particularly
among physicians, the statement detailed preventive methods and
provided an autheritative platform frr action by health departments,
..heart associations, medical societies, and other interested groups.
Today, a new, revised statement on rheumatis fover prevention
is being issued by the heart association with Public Health Service
cooperation. This new statement brings up to date knowledge gained
from research, much of which was supported by National Heart
, . Institute grants. For example, the statement contains recommendations
for the use of a new, long-lasting form of penicillin: several of
the researchers who worked upon this were supported by heart grantj: .
With the dissemination of the new statement. , there is an
occasion for an intensified endeavor in rheumatic fever prevention.
The Service and the /imerican Heart Association have developed and
are putting into effect new programs, particularly in professional
and public education, for this purpose; these form an important
- 20 -
part of activities for the yuar. New educational materials, such
as a new health education unit embracing a new motion picture and
leaflets for the public, form part of this strengthened, joint effort.
The public health opportunity for this is summed up by Surgeon
General Leonard A. Scheele as follows:
"Preventing rheumatic fever can save many more lives and
prevent or minim.i2e much more heart damage and disability that is
now being done, although there are underway in a number of communities
significant efforts in this direction. Many thousands of new cases
of rheumatic fever still occur each year, and there are many more
thousands of 'old' cases. An intensified campaign can markedly
change this picture and forestall much untimely death and suffering.
Here is a very real and great public health opportunity."
While space limitations preclude further detailo of this
activity here, full details can be supplied to the Committee if
In sum, th«re is underway today throughout the nation an
attack upon heart disease on research, public health, and other
fronts; this attack is of eonsiderably greater magnitude than a
few years ago and is progressing soundly, utilizing the opportunities
that arise from increasing knowledge to bring better and better
diagnosis, prevention, and treatment of heart disease. In the
"nationwide endeavor, the National Heart Institute, through the
■. support of the Congress, has developed as a major partner of the
physician, the researcher, and other workers in the field.
- THE END -
Dr. Robert H, Felix
Director, National Institute of Mental Health
Public Health Service
COMMITTEE ON APPROPRIATIONS
Mental Health Activltiss
Mr. Chairman £,nd Members of the CoEunittee;
The National Institute of Mental Health was authorized,
under the terms of the National Mental Health Act, Public Law 487,
(79th Congress) July 3, 1946, to provida for research relating to
psychiatric disorders and to aid in the development of more effec-
tive methods of prevention, diagnosis, and treatment of such dis-
orders. The first appropriation was made for fiscal year 1948
when a sum of iij>2,048,600 was made available to carry on these ac-
tivities. These funds were administered by the Public Health
Service's Division of Mental Hygiene, which had been established
in 1930 to carry on expanded activities under the Narcotics
Control Act. This Division was abolished when the National
Institute of Mental Health was formally established in April 1949.
As the activities of the National Institute of Mental Health
have begun to bear fruit in terms of promising research leads,
expanded training of professional psychiatric personnel, and sub-
stantive technical assistance to the States in the development of
control programs, annual appropriations for these activities have
gradually been increased. .
To carry on and expand the research already begvm, and to
support increased basic research and a newly instituted program of
clinical investigation at the Public Health Service's new Clinical
Center, a total of spl2,095,000 was appropriated for fiscal year 1954.
Additional support of training and research activities was
authorized for the cvirrent fiscal year, and funds for support of
laboratory and clinical studies at the Clinical Center were also
increased. The appropriation for the program administered by the
National Institute of Mental Health totaled ^14,147,500 for fiscal
NATURE AiO LXTLOT OF THE PROBLEM OF liENTAL ILLNESS
No quick, reliable and inexpensive method of determining the extent
of these disorders in the population has yet been devised. The best avail-
able estimates indicate that a minimum of 9 million persons are suffering
from mental or emotional disorders or mental retardation.
At the present time, our only exact measure of the number of people
in the United States who suffer from a mental illness or an emotional dis-
order or who are mentally retarded is found in the figures on the number of
patients who receive mental hospital care and treatment during the year,
and the n^ambe^ of patients in institutions for the mentally retarded. The
most recently completed tabulations (1951) show that nearly a million per-
sons are treated in mental hospitals and institutions during one year. Of
these 147,322 are mentally retaixied. It is assumed that approximately
600,000 patients are under care of outpatient psychiatric clinics or pri-
vate pJxsrsicians , Therefore, apparently a minimum of 7,400,000 people are
not receiving the psychiatric treatment or rehabilitation services that
Because a large majority of those who receive help obtain it in
public hospitals and outpatient clinics, the cost in tax funds is nmning
about ONE BILLION TM HUNDRED nILLION DOLLARS a year (including compensa-
tion to veterans with neuropsychiatric discharges), and the cost is increas-
ing at the rate of about one hundred million dollars a year.
Since records are kept on those under treatment in hospital, clinic,
or institution, it is basic to a better understanding of the nature of the
problem that information be compiled and analyzed so that we can evaluate
- 2 -
nvallable eervices, plan vrtsely for aAditlonal or new aervicee, aud find
out vrhat happens to these patients. Out Bioinetrics uuaff has "been en-
gaged for several years in working collaboratively irith the States to
develop euch Information.
To demonstrate the kinds of iniormation that can be obtained, the
Biometrics staff of this Institute cooperated with the Warren State-
Hospital in Pennsylvania on a study designed to find out what happened
to pationtB over a period of years — from I916 to 19^0,
The findings reeultine from this study are Intereetlng, encouraging
and cballeiiging to all irho are concerned irlbh the welfare of thoae who are
hospitalized for mental illness. They demonstrate that many of the men-
tolly ill can and do recover, can and do reeiune their places in the ooel.
iiiunity. This fact is of course well-known to the medical profession but
not nearly so widely understood by the public at large. The findings also
demonetrate that the length of hospitalization is being shortened for
certain typea of mental lllneee.
The Uarren State Hospital figuree ehow that the probability of
patients with, i'unctlonal peychosee (psychoeee for which no organlQ basis
can be found) being released vdthln the first year following aflxalaeion
to the hospital Increased considerably during the period 19^6-1950 over
what it had beea..in the preceding yeare beck to I916.
LABORATORY AND CLINICAL INVESTIGATIONS
At the National Institute of Mental Health, scientists of various
disciplines and various backgrounds devote their time and attention to
solving the problems of mental illness. The research program includes
both clinical and nonclinical areas of study. Pharmacologists, biochemists,
and physiologists v/ork together with psychiatrists, sociologists, and
Basic research is conducted in the Institute's laboratories. The
basic research studies, which also involve an interdisciplinary approach,
are concerned with investigations on the cellular or organ level, animal
behavior, mode of drug action, effects of social and environmental factors
on mental health and mental illness. In many of the research projects there
is collaboration between the basic research and clinical investigations
The Institute has organized three laboratories for clinical invest-
igations: the Laboratory of Adult Psychiatric Investigations composed of
the Acute Psychiatric Service and the Chronic Psychiatric Service; the
Laboratory of Psychosomatic Investigations, and the Laboratory of Child
Research with a group of schizophrenic patients on the adult services
is seeking to improve psychotherapeutic techniques used with psychotic
patients, and to find out more about the effects of specialized staff or-
ganization and ward management in the mental hospital. Special studies
are being conducted on biochemical and EEG (brain wave) phenomena observed
in the mentally ill.
- 4 -
- 5 -
Clinical Studies of Psychosonatic Illness
Physicians in general practice estimate that 40 to 50^ of all
their patients cone to then idth conplaintc that have psychiatric con-
plications. The Laboratory of Psychosonatic Investigations has been set
up to probe into the enotional factors v;hich play either a causative or
contributory role in the developnent of such illnesses as peptic -ulcer,
diabetes, high blood pressure, and certain types of heart disease. One
of the principal investigations in this laboratory involves an evaluation
of the different ways that norr.ial people, psychosonatic patients, and
schizophrenics respond to psycho logically- induced and drug- induced stress.
Fron this study, the investigators hope to detemine those factors that
are inportant in an individual's ability to withstand stress. The effects
of stressful life situations and the effectiveness of certain tranquiliz-
ing drugs on peptic ulcers are also under study, A study now being planned
will be concerned with the relationship betx\reen the severity of diabetes
and changes in personality.
Research on Schizophrenia
Because schizophrenia has filled nore hospital beds than any other
fonu of nental illness, much of both the laboratory and clinical research
is on the origin and treatnent of this widespread nental disorder. Scientist
studying nental illness are in general agreement that schizophrenia is prob-
ably not one disease \rith the sane origin for all people. For this reason,
studios of schizophrenia conbine the theory and nethods of a variety of
- 6 -
IJhile great strides have been nade in recognizing and diagnosing
the sjonptons of the disease, progress has been slower in treatment.
Intensive psychotherapy is the principal research ind treatment
nethod of the clinical investigators. Believing that the early relation-
ship between the mother and the child plays an important role in setting
the personality stage on which schizophrenia later develops, several
investigators are carrying on a study in which both the patients and
their mothers are admitted for treatment together. Early results indi-
cate that this arrangement allows treatment to proceed at an accelerated
pace. Confimation of this finding would mean substantial reductions in
the period of hospitalization and treatment of many schizophrenics.
Many biochemical and pharmacological studies have also focussed
on schizophrenia. Increasing attention is being given a number of chemical
compounds such as Rauwolfia serpentina , chlorproir.azine, and LSD (lysergic
acid diethylamide-25 ) . The value of these drugs in treating mental ill-
ness has not been completely assessed, but they have been an interesting
and useful research tool.
The Institute's clinical investigators report that there is some
evidence that Rauvrolfia serpentina and chlorpromazine are effective in
controlling and treating schizophrenic patients who evince considerable
anxiety and excitement. They have also obtained more information on the
action of LSD. This drug causes a psychological alteration in normal
people and produces a reaction in both acute and chronic schizophrenics.
- 7 -
The r.ianner by x\rhich LSD effects theso changes in r.ian is unknown. However,
when doses of thousand tir.:es greater than the r-j.nute aiuoiints given to nan
are given to luonlteys, a tenporary blindness results. This observation
suggests that the action of LSD nay be localized in an area or conponent
of the brain controlling vision.
LSD has also been useful in studying certain syr.iptons of schizo-
phrenia which nay be the result of an organic inpaiment. For instance,
schizophrenic-like reactions arc sonetir.ios the first signs of brain tunor
and diseases resulting fron nutritional deficiencies.
In addition to studies conducted by this Institute over the past
seven years, 56 research projects on schizophrenia have been awarded
grants totaling ^i)l, 965,000.
Two closely related projects which were aided over a period of
seven years were carried on by the coordinated work of psychologists,
psychiatrists and social workers. The studies were designed to describe
the schizophrenic personality in children five years of age and older
and in adults. Six patterns of schizophrenic traits and behavior ei-.icrged.
Each of these patterns provided a hypothesis for further study.
Sono of the inportant contributions of these two projects to
the general probleu of schizpphrenia nay be sunnarized as follows:
(1) nore effective tuchniques for recognizing schizophrenia, for differ-
entiating its sub-forns, for estinating the degree of schizophrenic
involvcnent, and for predicting the course of the disease in children;
(2) infomation on the relation between sone environnental forces and
the ripening of the overt synptons; (3) inferences regarding treatnont
- 8 -
that may be effective vith the specific form of schizophrenia under
On the other side of the coin, refinement of techniques for
estimating the degree of schizophrenia permits identification of the
residue of healthy functioning in the patient. This in tiorn provides
a foundation on which to base treatment.
The first volume reporting on this study was recently published
under the title THE SIX SCHIZOPHRENIAS, Reaction Patterns in Children
Research in Child Development
In one of the Institute's wards at the Clinical Center, a study
is being made of a group of emotionally disturbed boys of ages 8 to 10
who have presented serious difficulties to their families and communities.
Little is known about the treatment of such destructive and aggressive
children. No positive results have been obtained from the psychiatric
treatment which has been effective with shy, anxious children.
There has been a move throughout the country toward establishing
residential treatment centers for such children. The maximum effective-
ness of such centers, however, depends upon more knowledge about the
kind of life situation that leads to antisocial behavior and better ways
of helping the child make a satisfactory life adjustment. Treatment of
these children involves a study of all the contacts and activities in
the life of the child to determine their relative importance on his
total life experience.
In the brief period of four months since the boys were admitted
to the Center, progress has been made in treating them, and new data
which may prove of real significance are being developed.
- 9 -
Child studies have received major as well as continuous support
from the Institute's research grants program since its inception in
fiscal year 19U8. Over this period grants totaling $3^35^^000 have/awarded
to studies directly concerned with children. These funds represent over
2^% of the total research grant funds appropriated during the seven-
The Institute is supporting a wide range of research based on
the theory that the origins of some of the mental illnesses and behavior
disorders lie in the formative years of childhood. Most of these studies
are long-term, sometimes requiring 20 to 25 years to complete.
One of the earliest studies supported by this Institute has now
been completed, and a comprehensive report will shortly be published
under the title MIKffiST AND ITS CHILDREN, A Study in Psychological
"Midwest", a real town, is unique because it does not rely upon
nearby larger communities for its livelihood, services or recreation.
The project staff report that the town is the center of life for the
inhabitants and they actively participate in the life of the community
rather than assume roles as passive spectators.
Midwest provided a rich field for observation of how children
develop, behave, and learn to take their places in community life.
The Midwest study is basic research in human behavior and the psychological
factors affecting its development. Though ecological studies have tradi-
tionally been done in the biological and social sciences, this type of
study is unique in psychology. Because the mental illnesses and person-
ality and behavior disorders are characterized by difficulties in inter-
personal relationships and behavior, basic knowledge of the development
of behavior patterns is essential to our understanding of these disorders.
- 10 -
Another study receiving funds from this Institute in the first
year of the grants program has been completed, and the first of a series
of monographs on the work has been published under the title EARLY PHASES
OF PERSONALITY DEVELOPMENT, A Non-normative Study of Infant Behavior.
Prior to the receipt of our grant, several years had been spent in pre-
paratory work. The study itself required four years, and additional
monographs are still in preparation,
A great deal is known for the period of infancy about functions
presumably closely related to the process of maturing. However, there
is little factual information about the great variations among normal
infants in psychological development. This study conducted at the "iin
Wenninger Clinic in Topeka was designed to collect information on
individual differences in functioning assumed to be determined by
learning and by "constitutional" factors. One of the hj^jotheses studied
was that variations in infant development reflect significant differences
in the way in which the infant functions and the general adequacy of his
adaptation to the environment.
In order to study infants from a variety of socio-economic groups,
the research staff obtained the collaboration of the local public health
department and its Child Health Conferences,
Laboratory Research Programs
The Institute's laboratory research program encompasses a number
of disciplines, including neurophysiology, neurochemistry, pharmacology,
psychology, and sociology.
Fundamental studies of the activity of the individual nerve cell,
the interactions between these nerve cells, and the structure and function
of the brain as a whole have led to better understanding of the operation
of the nervous system. One study, involving the production of a labora-
tory phenomenon "spreading depression" in the cortex of a cat, has led
to improved brain surgery techniques and may be of great value in
determining the origin and nature of the various forms of epilepsy,
Physical chemists at the Clinical Center are studying the structure
of nucleic acids and their possible relationship to protein synthesis.
These studies are fundamental to other work on the role of nucleic acids
in heredity and the genetic factors in mental diseases.
Studies on cerebral circulation and cerebral metabolism have
yielded new information on the relationship between the local nutrition
of the brain and variations in states of consciousness or kinds of
mental activity. New insights have also been obtained on the factors
leading to the decline in function and structure of the nervous system
with advancing age.
The Institute's program in cellular pharmacology involves
fundamental investigation of the manner in wliich drugs and other
chemicals affect the metabolism and function of cells. This approach
should contribute greatly to a better understanding of the action and
use of drugs in man. Further studies of drug action in man, specifically
the effect of drugs in altering mood states, will also be important to
developments in psychotherapeutic techniques. If it is possible to
reduce an individual's anxiety or to increase his inherent assets with
drugs, the psychotherapeutic procedure of the future may be substantially
modified for certain individuals.
Research on animal behavior is essential to a program of mental
health research. Animals exhibit patterns of development and behavior
'wliich in many cases resemble those in man. Studies in monkeys' behavior
have expanded our knovrledgp' of the relationship between the nervous
system and behavior under varying conditions. Considtsrable information
has been obtained on the effects of brain lesion on learning and social
behavior and the development and extinction of neuroses. Results of
studies of the age changes in the behavior and structure and function
in the nervous system of rats are being applied to studies of aging
Psychotherapy, the irajor therapeutic device used in the treatment
of functional disorders, has been employed for many years, but no firm
knowledge has been obtained on why these techniques benefit some people
and have no effect on others. In an attempt to learn more about the
psychotherapeutic process, several of the Institute's investigators
are working out the experimental design for the recording and making
of films of a complete psychotherapeutic process with one patient.
Methods are being devised for the analysis and interpretation of the
data so as to improve the effectiveness of this treatment method.
Scientists examining the social and evironmental factors under-
lying mental illness have made progress, particularly in schizophrenia.
Several important phases of the Hagerstown, Maryland, study of
the distribution of schizophrenia mentioned in our report last year have
been completed by the investigators in the Laboratory of Socio-environ-
mental itudies. Contrary to somo current thinking, they have found that
social isolation during early youth and adolescence is a consequence
rather than a causative factor in the development of schizophrenia. In
related studies, these investigators have also confirmed previous findings
showing that the schizophrenic's mother has typically exercised very
strong authority, in contrast with the father's weak roiii io the family.
Increasing attention is being given to the contributions of biometric
research in the study of mental illness. The number of States participating
in the Model Reporting Area for Mental Hospital Statistics sponsored by the
Biometrics Branch has increased to fifteen, and it is hoped that two or three
more States will be able to join the Area within the next year or two. The
Model Reporting Area is designed to enable the States to work cooperatively
on the development of uniform statistical reporting which will permit mean-
ingful analysis and comparison. The information that will become available
through these joint efforts will extend our knowledge of what happens to the
mentally ill patient in the hospital, point out how his care and treatment
may be improved, and how the hospital may operate more effectively in the
interests of the patient. It will also focus attention on areas for further
The Biometrics Branch is also setting up a consultative service for.
the States in organizing new hospital and clinic reporting systems. Another
great stride has been the development of a nationid.de reporting system for
outpatient psychiatric clinics. These data will provide basic information
on the operation of this essential mental health facility.
In cooperation with the Warren State Hospital in Pennsylvania, the
Biometrics Branch made a study of outcome of treatment of first admissions
to the hospital. Based on the records of the Warren State Hospital during
the period 1916-50, the study provides information by different time periods
of admission on the probability of a patient of a given age and diagnosis
staying in the hospital, being released, or dying in the hospital. Such
facts are important in gaining commtmity acceptance of the mental hospital
as a dynamic, medical facility.
- 13 -
THE MEKTAL HOSPITAL
Today we are experiencing a newly-awakened public interest in the
therapeutic management of mental illness. One of the advances in thinking
in this field is the recognition that the mental hospital, whether well or
poorly run, is a therapeutic institution offering asylum in the best sense
of that word to those who are unable to live in the community. It will be
many years before we can hope to have sufficient professional personnel to
staff the public mental hospitals according to present standards, but there
is much that can be done to improve the therapeutic environment that the
As one method of expanding our limited resources, this Institute
has aided a study of mental hospital procediires and settings. A report
of the observations has just been published in a volume entitled THE MENTAL
HOSPITAL, A Study of Institutional Participation in Psychiatric Illness and
The study had three major objectives: to find out how the patients
live together; how the hospital works,* what might be done to make it work
better aiid speed the recovery of patients. The study demonstrates that
regardless of the Individual patient's history, at least some phase of his
illness is affected by the functioning of the hospital as a social unit.
Other mental hospitals may be challenged by this study to take a look at
their own policies and procedures and find out whether there are ways to
improve them for the greater benefit of the patient.
GROWING DEmi^lD FOR MENTAL HEALTH SERVICES, TRAINING,
The upsurge of interest in the problem of mental health has sharply
increased the demand for services to individuals, for research, and for train-
ing increasing mi.Jj^ rs of professional personnel. The history of this growing
interest can be summarized briefly.
At the direction of the annual Governors Conference, the Council of
State Governments cooperated with the States in making and publishing two sur-
veys: CENTAL HEALTH FROGRAMS OF THE FORTY-EIGHT STATES, and TRAINING AND
RESEARCH IN STATE MENTAL HEALTH FROGRAMS.
In February of last year, the first National Governors Conference on
Mental Health was held in Detroit. A 10-point program adopted there set goals
for the States in developing more adequate mental health services, in expand-
ing trrining opportunities and in initiating or expanding research programs.
The Southern Governors Conference, of which 16 States are members,
directed the Southern Regional Education Board to survey the training and
research resources, existing and potential, and report back to the Conference.
With the aid of a grant from the National Institute of Mental Health, the sixr-
vey of resources in the 16 States was completed last summer. The November
meeting of the Southern Governors Conference adopted recommendations for con-
crete action by the member States individually and through inter-State com-
pacts. As the program develops, graduate students will be able to receive
their professional training in their own or a neighboring State where their
skills are so greatly needed for services, teaching and research.
Similar regional programs are underway in the New England States, the
Midwestern States and the Pacific Coast area. These actions on the part of
the States demonstrate the deep interest of the public in moving more rapidly
on all fronts. However, the movement is necessarily geared to the availability
of trained personnel, now in short supply.
_ 1 K _
- 16 -
Incr e asing the Supply of Trained Perao nnel
Through grants to universities and other training centers to stimu-
late the expansion of training programs and provide traineeships to
graduate students, the National Institute of Mental Health is providing
concrete help toward the achievement of clearly defined objectives.
In developing the training grants program with the advice and
assistance of the non-Federal experts who constitute the National Advisory
Mental Health Council and its Training Committee, choices had to be made
to use our resources as effectively as possible. Taking first things
first, our efforts were directed toward strengthening the training and
increasing the number of trained people in the basic mental health pro-
fessions—psychiatry, clinical psychology, psychiatric nursing and psy-
chiatric social work.
Today, there is a crying need and a growing demand not only for
people from these professions, but for people qualified to work on prob-
lems which constitute subspecialties of the broad mental health problem —
juvenile delinquency, mental deficiency, alcoholism, drug addiction, the
problems of aging, the problems of mental hospital administration and
The Institute staff are working with the universities and other
training centers on some of these subspecialties to define the training
program needed and facilitate its development. One of the projects under-
way is focused on the preparation of mental hospital administrators. The
goal is to design the kind of; training program the physician needs to
promote maximum effective use of mental hospital services.
- 17 -
The training of professional personnel to work with the mentally
defective individual and his family is also of paramount importance. Many
of these retarded children can be helped to become self-sustaining members
of the community if their handicap is diagnosed at an early age, their
abilities and limitations carefully assessed and appropriate training
given to them. Others with more severe handicaps can be helped to lead
a more satisfactory life in the limited area in which they must live.
Training for the mental health field, therefore, not only becomes
a matter of training in the four psychiatric professions but includes
special training in psychiatric concepts and the dynamics of human be-
havior for professional people who are immediately concerned with some
of the problems previously enumerated as "sub- specialties." Such special
training by its very character adds to the nimber of people who can make
a real contribution in the broad spectrum of community mental health
State and Community Services
The ultimate objective of all efforts in research and training
is to provide new knowledge, new techniques, new skills and well-quali-
fied professional personnel to the States and communities throughout the
country so that mental illness may be controlled, and sound mental health
fostered in every individual.
Before the passage of the National Mental Health Act, there were
only 24 States which had mental health programs, though all 48 States
had to provide hospitals and institutions for the care of the mentally
ill and the mentally retarded. Today all 48 States, the four Territories
and the District of Columbia have mental health programs in addition to
- 18 -
hospital service. Because many of the programs were so recently created,
they are in various stages of development.
In fiscal year 1954-> a total of ;i)15, 000,000 was available to the
States for community mental health services of which i,'p2,325,000 repre-
sented Federal grants, and Cp2, 270,000 were private funds.
In the current fiscal year, withthe same amount of Federal grants,
22 States and Territories have the same amount of money they had in 195Aj
2-4 reported an increase of 10^ or more over 1954 and 7 States had a de-
crease of 10;>^ or more. Five States and the District of Columbia have
budgeted a total of nearly ^600,000 for alcoholism treatment and con-
The Community Services staff at the Institute and the psychiatric
consultants assigned to the Departmental Regional Offices handle as many
requests for professional consultation and technical guidance from the
States as they can. However, the new impetus to these programs from the
actions of the various State Governors conferences and State legislatures
have greatly stepped up the number of requests received. There is, in
addition, need to develop nev/ techjiiques for providing mental health
services more effectively and for demonstrating control techniques.
Dr. Victor H. Haas
Director, National Microbiological Institute
Public Health Service
COMITTEE ON APPROPRIATIONS
"Microbiology Activities, Public Health Sorvico"
'-'.Tt Chairman and Members of the Committee:
The National MicrobiolO;'i;ical Institute was created
in 19)i0 by consolidating those labor/itories within the
National Institutes of Health which conducted .research on
the infectious and parasitic diseases. These laboratories
were the oldest in the Institutes, some having been in
operation from the very beginnings of the original Hygienic
Laboratory. Scientists workin;;; in these laboratories, and
in the Institute of which they are now a part, have made
many significant contx'ibutions to the advances in the diag-
nosis, treatment, control, and prevention of the infectious
and parasitic diseases, A program of clinical investigation
was added in Fiscal Year 19Sh) and grants in aid of research
in appropriate fields are administered by the Institute,
Under the 1956 budget, the National Microbiological
Institute will operate at essentially the same level as in
Fiscal Year 1953'. Small increases are requested chi'..;fly to
provide for activating additional beds i.n the Clinical Center
and an accelerated poliomyelitis vaccine testing program.
Scope o f Mic robiolo fjy
Microbiology is the study oT microorganisms: viruses, rj.ckcttsiae,
bacteria, fungi, protozoa and parasitic worms. In the National Micro-
biological Institute attention is focused on tliose species vrhich cause
human disease. In practical application, microbiology embraces also
the study of animals which serve as hosts and vectors of disease-produc-
ing microorganisms. Such animals include insects, birds, aquatic animals,
and mammals, one of the latter being man.
Mag;nitude of Infectious and Parasitic Diseases
In the United States, the majority of illnesses are caused
by microorganisms. This is true in spite of the phenomenal advances
in prevention and treatment of infectious and parasitic diseases
which have marked the present century. The common cold, and similar
infections of the upper respiratory tract, are still the most
widespread and frequent of all diseases in this nation. Diseases
of the gastrointestinal tract — particularly the infectious diarrheas-
are only a little less common. Our children (and their parents) must
still suffer through many of the common infections which their an-
cestors have had to bear since the beginning of history, e.g.
measles, mumps, chickenpoX;, bronchitis, bronchopneimonia, polio-
myelitis. Though many of the killing infections can now be pre-
vented, treated, or controlled, there remain many microorganisms
which have stubbornly resisted all our modern methods and drugs.
People in the United States still die of pneumonias, urinary tract
infections, streptococcal disease, virus infections, diseases pro-
duced by fungi, and other infections and parasitisms which we are
often powerless to deal with. Even leprosy, the scourge of Biblical
times, has not been eliminated from our country, and often resists
even our most modern treatment.
Abroad, many diseases weaken or kill our friends and allies^
from time to time some of them cause us grave concern because of
their possible introduction into this country. The current year
- 3 -
has seen some startling developm3nts in the spread of yellow fever
northward through Central America and into Trinidad. The best
scientific minds of our time are mystified at the way in which
a great epidemic disease will sometimes appear dormant for decades^
and then suddenly undergo a sharp and ominous recrudescence,
A research attack on the microbiological diseases that
continue to impose a crushing burd-.^r. of suffering, despair and
economic deprivation is a matter of direct interest to this country
for several reasons. First, as noted above, there is the problem
of preventing the introduction or a reintroduction of some of these
diseases into this country. Second, the study of agents causing
these diseases is intervroven with the whole body of research in
microbiology. Third, we have troops in most parts of the world,
and the regions in which heavy troop movements may be necessary
cannot be predicted. Fourth, research can increase the physical
ability of large population groups to do a full day's work. This
vjill enhance the economic position of underdeveloped countries
and redound to the benefit of this country. Fifth, medical re-
search devoted to solution of the major disease problems of these
countries is a potent and feasible means of winning friends through-
out the world.
Program of the National Microbiological Institute
The program of the National Microbiological Institute is based
upon fundamental studies of the physiology, metabolism, and genetics
of microorganisms, and upon investigations of the effects which they
produce upon the cells, tissues and organs of the animals (particular-
ly man) which they infect. It extends beyond fundamental studies in
- l4 -
the laboratory, providing opportunitins for skilled scientists to
follow up the leads from basic research by experimental trials in
the field, the community, the clinic, and the hospital ward.
Progress in microbiology is continuing at a fast pace. With
years of sound achievement behind them, scientists in the Microbio-
logical Institute are confidently looking forward to exciting new
discoveries. New knowledge and techniques are constantly being
applied to problems in the infections and parasitic diseases which
thus far have eluded solution. Fundamental information on the effect
of microcrganisms on the intimate biological mechanisms of the infect-
ed cell is rapidly increasing^ it v/ill have practical significance
far beyond the problems of specific infectious diseases.
Advances and Problems in Research on Viruses
There has been a great surge forward in the field of virology
during recent months. The viruses are the smallest forms of lifej
indeed, it is questionable whether they are completely living in
the sense that higher organisms are. They produce many diseases in
man, and are in the aggregate responsible for more illness in the
United States than any other disease-producing agent, or group of
related agents. In particular, they rauao many of ftu? jllno^sos
of children, some of which piuduce permanent disability. Virus
diseases include the common cold, influenza, poliomyelitis, measles,
mumps, German measles, encephalitis, and some types of pneumonia.
The sturi^'- o.f vji'uses, originally stimulated by use of the
chick embryo, was further facilitated a few years ago by use of
immature rodents (mice, rats, hamsters) for producing the necessary
quantities of relatively pure virus in the laboratory. During the
- 5 -
year just past, there lias been an enormous development of tissue
culture techniques for this purpose. Not only has the method
proved far better than anything previously available, but practi-
cal results have materialized rapidly.
One of these, the development of experimental vaccines against
poliomyelitis, has been the outstanding accomplishment in the infec-
tious disease field during the past year. This has been a long
step forward in our attack on this crippling infection. Scientists
of the Microbiological Institute have been active in this field for
many years. The transmission of poliom3''elitis to mice, accomplished
by one of the Institute's scientists, initiated the current wave
of progress in poliom.yelitis research. Another significant and
more recent contribution was the discovery that virus could be
successfully established by direct inoculation into the spinal
cord of the mouse. The testing of one of the present experi-
mental vaccines for safety and potency has occupied a consider-
able part of our resources during the current year, and technical
methods are now being developed for assuring both the safety and
the potency of commercially-produced poliomyelitis vaccines which
are quite likely to appear xfithin a few months.
Another advance in the virus field has occurred in respect
to the viruses lA'hich inliabit the respiratory tract of m,an. The
Institute's scientists and other investigators supported by N'MI
grants have been leaders in this work, and are now isolating and
studying many nevj viruses of this sort. Some are being inoculated
into hum.an volunteers, and recently completed investigations indicate
that these studies are already leading to more exact recognition of
- 6 -
the nature of soma of the "fevers of undet^^rmined origin." The
tool which has made these advances possible has been tissue culture;
the combined skills of the laboratory scientist, the clinical inves-
tigator, and the epidemiologist have forged the successful product
of this research. One clear-cut epidemic has been studied thorough-
ly enough to permit the clinical definition of a specific disease
not hitherto identifiable, the isolation of the causative virus,
and the demonstration of antibodies in the blood of persons after
recovery from infection.
The viruses of this now group have been named APG — for
adenoidal, pharyngeal, and conjunctival, referring to bhe fact
that they are recovered from these particular tiscues (nose, throat,
and eyes) of man.
Concepts about viruses are being clarified. Scientists are
learning that there are many more viruses than anyone has hereto-
fore suspected. Some of them apparently inhabit man foi' long
periods without producing disease. A number of them can be demon-
strated only after prolonged growth of human tissues outside bhe
body. Yet under some circumstances, viruses of this sort can cause
illness and even widespread epidemics. The Institute's scientists
and independent workers supported by research grants from the Insti-
tute are now making significant contributions to this new knowledge
of how viruses can behave in such different ways.
Progress of this sort generates still greater progress.
Problems in virology that have long awaited solution are being at-
tacked vigorously. There is no satisfactory treatment for virus
diseases, and no adequate means for preventing many of them. The
- 7 -
new understanding of how viruses behave, and what influences
changes in their behaviour, provides a rational means for attack-
ing the diseases produced by these agents in man. Beyond this
immediately practical goal, scientists are getting flashes and
glimpses of now comprehension in regard to the basic relationships
of the virus and the cell which it inhabits, and of whose intri-
cate life processes it must at one stage of its development become
an inseparable part. The not too distant goal is an accurate
understanding of what can cause a cell to go wrong, and how.
Whien scientists can tell this, the answer will have a profound
effect upon our conquest of human illnesses, far beyond the infec-
tious and parasitic diseases.
Research in Parasitic D isea ses
While progress in virology is leading the field in micro-
biology, there are advances in other areas which promise to be
useful in the ultimate control and treatment of many infectious
diseases. A promising field for research, which the Microbiological
Institute has now entered, concerns the effect of bacteria and
other such micoorganisms upon the larger parasites of the protozoal
group (single-celled animal parasites). Preliminary results indicate
that parasites which ordinarily produce disease may be harmless in
experimental animals vjhich are entirely free of other microorganisms.
One of the least understood areas in microbiology concerns the way
in which various microorganisms antagonize, interfere with, or
augment one another. The recent observations on germ- free animals
add another substantial segment to the structure of organized know-
ledge now being built up about this problem. Ultimately, it will
- 8 -
be possible to use microorganisras more and more to man's advan-
tage in the conquest of disease^ this has already been accomplished
in the field of antibiotic drugs, and in agricultural and many in-
Opportunities are increasing for defining the causes of
many diseases of previously unknown origin. Recent vjork has shox-/n
that the parasitic protozoan known as Toxoplasma is res;DonsiblG
for many cases of a serious eye disease (uveitis) which often re-
sults in blindness. This cui^ious microorganism is widely dis-
tributed in lower animals; it is capable of existence in man with-
out producing disease, but under circumstances stil], to be explained
can cause severe illnesses in addition to the eye conaition just men-
tioned. The prevention of those disabilities depends upon acquiring
more knowledge about the parasite, how it gets into the human, why
it sometimes causes disease and sometimes does nob. Since the
greatest danger is to the unborn child of a mother who harbors
the parasite temporarily, and x\rithout any c^vidence of infection,
control and prevention of damage must be based on fundamental under-
standing of the life history of the Toxoplasm.a.
While the broad problem is under intensive study, scientists
in the Microbiological Institute have recently made two discoveries
of very practical significance. One was the demonstration of the
organism, in certain diseased eyes, thus proving its association
with the affliction it had been suspected of causing. The other
was the successful employment in a human case of treatment pro-
cedures developed in laboratory experiments with animals. The
National Institute of Neurological Diseases and Blindness has.
- 9 -
as will ba reported, studied other aspects of this disease.
Congenital In fe ctions
Another cause of damage to the unborn child was found
several years ago to originate from German measles, a normally
mild disease. These two examples of serious harm to a child still
in the uterus suggest that other infections, as yet ujirecognizod,
may cause similar disaster. This problem is receiving more consid-jra-
tion as a result of the disclosures about toxoplasmosis.
An intriguing experimental observation reported by Institute
scientists in the past year indicates that in.fection of the mother
during pregnancy influences the ability of the offspring to develop
protective antibodies in response to infections acquired after birth.
This phenomenon, demonstrated in laboratory animals, emphasizes further
the potential influence of infections upon the unborn child.
There are many congenital illnesses and abnormalities whoso
causation requires explanation; investigators wj th our now clinical
program are studying some of those conditions with a view to clari-
fying the possible role of infections.
New Opportuni ties in Microbio logy
Never before have scientists in microbiology so expanded
their interests beyond their own fields of personal specialization.
This is a good omen for progress. The virologists are becoming inter-
ested in problems ranging from parasitology to cancer; parasitologists
are working across their usuil boundaries to contribute to basic cellu-
lar biology and biological interrelationships of microorganisms;
epidemiologists are applying their talents to the identification of
illnesses of unknown causation. The physiologist and the geneticist
- 10 -
find intriguing opportunities in bacteriology 'md virology. The
clinician turns from the bedside to the tissue culture laboratory
in his attempt to define a patient's illness and to treat it most
effectively. As basic knowledge increases and comprehension
widens, scientists in microbiology arc beginning to develop common
goals vjhich can be perceived by many vrorkcrs with different training
and backgrounds. As these goals are 'ipproached from many points of
departure, they become clearer, and their attainment j.s facilitated
by the exchange of information derived from the different points of
The m.omentum of present advances in microbiology is influenc-
ing scientific research throughout medicine and public health. The
results now coming froin the laboratories — and those anticipated in
the future — will not only widen enormously our comprehension of man's
relationships with the teeming microscopic life about hiia and v.dtliin
him, but will surely enable us to achieve mastery over many illnesses
as yet unconqucred.
Dr« Victor !!« Haas
Director, National Microbiological Institute
Presented in Behalf
Gorgas Memorial Laboratory
COM"IITTEE ON APPROPRIATIONS
Gorgas Memorial Laboratory-
Mr, Chairman and Members of the Committee:
The Gorgas Memorial Laboratory, research branch
of the Gorgas Memorial Institute of Tropical and Pre-
ventive Medicine, was established in Panama to serve
as a permanent home for the Laboratory, which was
named for General Gorgas in recognition of his many
contributions to the control of diseases prevalent
in the tropics. The Laboratory was set up in Panaraa
so that the benefits of its research might be applied
primarily to the prevention of tropical diseases in
the population of the Republic of Panama, the Canal
Zone personnel, and the military forces stationed in
An annual appropriation to finance the Labora-
tory's research progr.ara has been made by the United
States Govornraont since 1929. Because these activi-
ties had been greatly expanded during World ¥ar II
and because a number of projects of special interest
to the Army had not been completed. Congress amended
the original Act in 19li9. The authorized amount
which could be appropriated annually was increased
from the original 050,000 to a figure not to exceed
One of the major studies of the Gorgas Mem.orial Laboratory
concerns jungle yellow fever in Central America, This disease,
absent for decades, appeared in Panama in 1914-8 in epidemic form
and has since spread northward as far as Honduras, Present
indications are that jungle yellow fever will continue its
prosont course and perhaps reach Mexico,
The past year has also seen the occurrence of yellow
fever in the northern part of South America and the Island
of Trinidad, off the coast of Venezuela, Health authorities
in Trinidad met the threat by laiinching an intensive program
to vaccinate the entire population.
The Laboratory's yellow fever studies, initiated in
19^1f are aimed at determining the insect carrier or carriers
of the virus in Central Americaj whether animals other than
monkeys might serve as reservoirs for the virus j and how the
virus survives through the dry season when the known mosquito
carriers are not present. In this program the Central American
countries concerned are supplying excellent assistance to the
Gorgas Laboratory, and the Pan jlmeri.can S,anitary Bureau is
also actively interested in the yellow fever work. In the
United States, health authorities arc concerned with the dir-
ection of spread of yellow fever because of the fact that our
Southern states contain species of mosquitoes capable of trans-
mitting the disease.
Malaria control studies by the Laboratory have shown
that the response of mosquito carriers to DDT -treated houses
may point to important changes in the malaria situation.
Mosquitoes now observed in treated villages are hyperactive
■■■■■ <?■.';■• iACif::i;;:
and apparently do not remain on the treated surfaces long
enough to obtain lethal dosages of DDT, Plans have been
made to study this peculiar phenomenon, but the Laboratory
has been \inable to start investigations because of the pres-
sure of the work on yellow fever« It is worth noting that
laboratory tests have demonstrated that mosquitoes caught
in dwellings are still just as sensitive to DDT as those
maintained in the insectary and never exposed to DDT,
Inasmuch as DDT spraying of living quarters is now
being wj.dely employed in manj^' parts of the world to control
malaria, the Laboratory's findings on the reduced effective-
ness of DDT are of great interest to health authorities every-
where — particularly in view of the fact that the pi'oblem con-
cerns factors other than the emergence of DDT-resistant
mosquito populations. The Laboratory is also cond\icting an
antimalarial drug testing program among natives, but this
work has not been under way long enough to report on its
Studies are continuing on leishmaniasis, a disease
which is prevalent in Latin America and many other parts of
the world. Since the work began, the Laboratory's scientists
have built up a collection of sandfly specimens embracing 60
species. As a result of this work new knowledge has also been
acquired concerning other biting insects in the area.
■■^"-'f'i,,;-, -, ,.,.
Under its present leadership^ the Gorgas Memorial
Laboratory hopes to expand its virus work and to establish
a registry of pathological spociinons on the tropical diseases
of the area, as well as continue its present activities.
During the past year, a careful study of the Labora-
tory's program was made by a United States committee at the
request of the Surgeon General of the Public Health Service »
The commd.ttce unanimously recommended that the Gorr^as Labora-
tory be continued in operation. This opinion was based on
the substantial accomplishments of the Laboratory over a
period of years — accomplishments all the more remarkable in
view of the small amount of money e:q3ended in its operation.
The committee felt that the Laboratory is conducting a vig-
orous program, and under appropriate leadership should have a
Dr. Pearce Eailey
Director, National Institute of Neurological Diseases and Blindness
Public Health Service
COI'MTTEE ON APPROPRIATIONS
"Neurolog7 and Blindness Activities, Public Health Service"
The National Institi.te of Neijrological Diseases and Blindness
is the youngest of the National Institutes of Health, having been
established by Public Law 692, August 1950. No appropriation, however,
was mads to activate the Institute until fiscal year 19^2, when
$1,250,000 was made available to initiate a beginning program of
research in the broad field of neurological and sensory disorders.
These funds v>rere allocated within the general appropriation "Operating
Expenses, National Institutes of Health, P.H,3. 1952."
During fiscal year 1953, '/l,9'''2,rC0 was appropriated to pro-
vide for essentially the same program as the previous year, the bulk
of the funds going to the support of research activities in medical
schools and universities.
To fijrther the original plans of the Institute, to capitalize
on expenditures to date, and to begin to meet the rising urgency of
more research in this relatively neglected area, the fiscal year 195U
appropriation of '[1,500,000 carried, for the first time, the National
Institute of Neurological Diseases and Blindness as an identifiable
In fiscal year 1955, the Institute's appropriation was raised
to $7,600,500 thereby permitting extension of its programs in clinical
research and in research training.
Mr* Chairman and Members of the Committee:
mTURE AND INCIDENCE OF THE NEUROLOGICAL Affll SENSORY'"' DISORDERS
The seriousness of the neurological and sensory dis-
orders as a public health problem has been made known to
^'^Disorders of vision and hearing
Congress in previous years. The salient facts are these:
1) Some 20 million persons in the United States are affected
by some 200 of these condi.'ions. The most familiar,
though not necessarily the most serious, of the neuro-
logical disorders include cerebral palsy, muscular
dystrophy, epileps;/', multiple sclerosis and cerebral
vascular disease (stroke) 3 the most familiar sensory
disorders include glaucoma, cataract, uveitis and
2) These disorders are the third leading cause of death
in the United States and the first cause of permanent
disability: some 10 million victims are gravely
crippled by these conditions.
3) The vast majority of these disorders are incurable and
only a few are treatable.
The degree to which these disorders affect the public interest
economically has not always been evident. It may seem obvious that
vxhere a vast number of persons are disabled over a large, if not
total, portion of the normal life span, their care and welfare must
place a special r.- economic burden on society. But only recently has
some documentation of the relative costs of the neurological and
sensory disorders begun to emerge. This has been made possible by
a study still in progress under the auspices of the NaTiOWj-iL COlilJlTTElii
FOR KESLaKCH in NiiUrtOLGGICiiL DISORDERS.-'''
The studj' initiated by the Committee is still incomplete, and
the facts presented here represent only a portion of those which will
illuminate to what extent the neurological and sensory disorders
''""The National Committee for Research in Neurological Disorders has
been mentioned before Congress in past years. Composed of representa-
tives of the leading voluntary health organizations in the field, it
now acts as a unifying force for defining research needs and development
throughout the nation. Its constituents include the National Society
for Crippled Children and Adults, United Cerebral Palsy Association,
National Epilepsy League, United ILpilepsy Associations, National Multiple
Sclerosis Society, National liuscular Dystrophy Associations, and the
American Academy of Neurology.
- 3 -
presently constitute a burden to the Federal Government and the
forty-eight States. The data herewith presented represent the
Committee's analysis of statistics published by the Bureau of
Public Assistance, the Office of Vocational Uehabilitation and the
Tm TOLL TAILM BY THL ili.UKOLOGICAL Ai'ID Si.NSOHY DISORDERS
In 19$1, some 200,000 persons with various disorders were
receiving public assistance funds from the majority of States, Of
these, more than half , or more th;in all persons with all other
disorders combined , were victims of the neurological and sensory
disorders. The average cost of their assistance xms more than
Not including the blind (also the research responsibility of
the Institute), i.who receive almost as much assistance as recipients
suffering all other conditions, the numbers of those with neurological
disorders alone ranked second (29 percent) only to heart disease
(31.9 percent). It is noteworthy, however, that heart disease was
only more prevalent in the age group ip$ or over. In the two other
age groups, 35 and under and 35 and over, neurology patients ranked
first with 51.3 and 35.U percent of the total respectively.
These last statistics suggest that neurological patients are
long-term patients, and indeed tius is confir'med by the fact tliat
these patients represent U6 percent of the total (more than any
other group) who had endured their disabilities for a period of 10
years or more.
- u -
The personal and family trageuy, including the economic drain,
involved in these disorders is also revealed in analysis of the
statistics indicating the numbers of those on public assistance who
were bedridden, chairfast or housebound. In these areas, the neuro-
logical disorders oven^helmingly represented the leading cause for
total removal from the social and economic scene with Ul.l percent
of the bedridden, ^0,5 percent of the chairfast and 35 percent of
The pex-sonal degradation caused by these disorders could also
be measured by statistics, for neurological patients represented
6U.8 percent of all those needing aid in eating, $$.h percent of
those needing aid in dressing, and 55.1 percent needing toilet
I'Jhile the facts and figures on persons receiving public
assistance are the most complete, data from the Children's Bureau
and the Office of Vocational Piehabilitation present substantially
the same picture of overwhelming need on the part of those suffering
the neurological and sensory disorders. Of the more than ,pU2,000,000
spent by the States and Federal Government for services to children
with a variety of disorders, more than k6 percent was allocated for
aid to children disabled idth cerebral palsy, epilepsy and other
disorders of the brain and spinal cord, and disorders of the eye
Of lj.8,983 receiving vocational rehabilitation in 1953 (not
including somewhat more than 12,000 persons receiving such assistance
- 5 -
because of unspecified accidental injuries) j 11^308 or approximately
2k percent X'/ere victims of the neurological and sensory disorders,
more than any other single category. It is perhaps appropriate to
mention tliat many patients idth these conditions cannot be candidates
for vocational rehabilitation because their diseases are progressive
or because crippling is so severe as to make useful vocational train-
THE. SCIENTIi^C aTTaCK ON THE liEUhOLOGIGAL AiTO SENSORY DISORi^EuS
To the major problem posed by the neurological and sensory
disorders, science has only recently bi'ought to bear its Irnowledge
and desire. The reasons for delay have been mentioned before; among
them, the reluctance of the crippled victim to press for aid where
such pressure might only call attention to his disability , not his
need; and the reluctance of science to challenge the vast complexities
of the central nervous system where more open pathways of productivity
lay before him and, more important, xirhere funds were available to
The growth of the voluntary health organizations in this field
has been central to ansvjering both of these problems. These agencies
could speak and bring care for the victims. They could even provide
some support ior the scientists. Ith the gathering accumulation
of knowledge about the nervous system and with the development of
new tools for the exploitation of further knowledge, the way was
cleared for a full-scale attack on the neurological and sensory
- 6 -
The first major vehicle foi" this attack, however, only came
with the establishment of the National Institute of Weurolo;_ ical
Diseases and Blindness in 19^0. As the first national Institute
devoted wholly to research and research training in the neurological
and sensory disorders, there can be no question of its significant
role in medical history,
SUCCESS OF THE .hTThCK '
In last year's testimony, some sure signs of that role were
already indicated. The first important increase in appropriations
for fiscal year 19Ii>3 had been marked by a comraensurate rise in the
Institute's productivity and tlie productivity of its grantees, ihile
increased support and increased scientific productivity can never be
in direct correlation, the Institute is again pleased to inform
Congress that the increased appropriations for 19!^U were again
followed by research achievements of a high magnitude.
It is perhaps significant that of some forty "highlights" in
medical science of the past year as appraised by Science Service (of
vrhich only twenty were concerned with medical research), Institute-
conducted or supported research was represented by four accomplish-
ments. In terms of individual health and the national economy, \je
feel these four achievements the most important. They are;
1) A m.ethod for the almost total pi-evention of retrolental
fibroplasia, the leading cause of blindness in children.
2) A method for the treatment of granulomatous uveitis caused
by toxoplasmosis, a disease responsible for from 5 to 7
percent of blindness in adults.
- 7 -
3) A method for the improved treatment of acute and chronic
glaucoma, thereby aiding in the control of a disease
responsible for 20 percent of all blindness.
h) The further development in the treatment of epilepsy by
glutamine and asparagine.
Last year, the Congress was inform.ed that discovery of basic
metabolic defects responsible for epileptic seizures had been .made .
by an Institute scientist. This discovery provided the first rational
basis for the treatment of epilepsy and opened up nex-/ avenues for
research on the brain.
Of three metabolic defects, it was considered that the epileptic's
inability to maintain glutamic acid at normal levels within the brain
cells was probably the most important. On the basis of this considera-
tion, experimental therapy of epileptics V7ith glutamine (the amide of
glutamic acid) and asparagine, a closely related compound, was insti-
tuted. The results of tliat experimental therapy on several patients
x-rith frequent, uncontrollable seizures were made known to Congress i
seizures were greatly reduced or eliminated and the epileptic EEG
patterns often were improved.
On the basis of this discovery, the Congress in June 19Sh
appropriated ^750, 000 for a more intensified investigation of glutamine
and asparagine so as to obtain a more decisive answer as to their
efficacy in controlling epileptic seizures. These appropriations
permitted the purchase of these expensive compounds in amounts which
would allow for expansion of the study at the Clinical Center and for
the award of grants for similar studies at other institutions. All
- 8 -
studies -rwould. encompass enough patients in total so that results at
the end of a yeaf might be considered statistically adequate.
At this point, the elaboration of the glutamine-asparagine
studies are well under way. Five medical schools now are participa-
ting in this collaborative effort for a year's period.'" Their clinics
and hospitals are assessing asparagine therapy on a total of 100
patients with all types of epilepsy; they are working under a single
research protocol formulated by the Institute but reviewed and agreed
to by all investigators in careful discussion.
The Institute's OTcjn assessment of glutamine-asparagine therapy
at the Clinical Center has been expanded to a total of twenty-four
patients, only two of vihom, however, have received treatment for a
year; two for more than six months, A total of fourteen have been
on either or both compounds for at least two months, and on the basis
of data now at hand, there is no reason to revise our feelings of
optimism as indicated last year.
All fourteen epileptics have been victims of frequent, persis-
tent seizures, ranging from one to fifty attacks a day. A variety
of anti-epileptic medications have failed to control these attacks.
Under asparagine aand glutamine treatment, however, three patients
are essentially seizure-free, nine have had their attacks reduced by
60 percent or more, and only t\iro show equivocal responses. As a
*See appendix A for participating medical schools and investigators
- 9 -
result, some child patients have been able to resume schooling (one
boy having been saved from institutionalization) and adult patients
have been able to secure and maintain gainful employment.
AS mentioned last year, we found that glutamine and asparagine
were easily absorbed into the brain. In establishing maximum thera-
peutic dosage schedules mth any medications, it is essential to
evaluate their degree of concentration in the body. Therefore, part
of our basic research is devoted to determining the concentration of
glutamine and asparagine in the bloor' and spinal fluid. We shall
expect to have refined a practical method for this test within the
next six months.
Last year, the Congress vras infomed of the Institute's
special capacity to meet special research needs as they occurred, and
the Institute's initiation and support of a broad collaborative study
of retrolental fibroplasia was cited as one such case. This clinical
study, finally encompassing more than seventy-five investigators
working at eighteen hospitals, had been established in order to confirm
or deny striking animal experimentation conducted by an Institute
grantee. Its breadth had been compelled by the urgency for obtaining
as rapid and decisive an answer possible to a serious problem.
Retrolontai fibroplasia, a progressive disorder of the blood vessels
of the retina, primarily occurring in premature infants weighing
3-| pounds or less at birth, has caused some 8,000 cases of total
blindness since the disease was first reported in 19U2 by Dr. T. L.
- 10 -
The preliminary findings of the retrolental fibroplasia study-
have now emerged and there can be little doubt that the results con-
stitute the most important single clinical advancement in ophthalmology
during the past decade. Announced last September at the annual meet-
ing of the iimerican Academy of Ophthalmology and Otolar^Tigolof.y, tne
findings v/ere unequivocal that oxygen - the o.:<ygen routinely adminis-
tered to premature infants in their incubator - was -'.efinitely
associated i-ri.th the cause of retrolental fibroplasia and tiiat ox^/pen,
thei^efore, sliould be administered to premature infants only in times
of severe clinical crisis.'""
The results of this study have been made Icaown to piiysicians
and hospitals throughout the world. Because some children v/ill still
have to receive o^cygen for clinical crisis, a fevf will probably still
incur retrolental fibroplasiaj a few othtrs ijiil develop the disorder
for causes still to be explored. On the basis of results so far
announced, however, only about 10 percent of those who suffered it
in the past will suffer it in the future.
The cost to the Govex''nment of this study totalled >l|0,000,
and another ;>11,000 was added by tiro voluntary agencies. The 8, JOO
children already blinded by retrolental fibroplasia will, during
the course of their normal life span, cost the States, the Federal
Government and several welfare organisations ;^i)100,000 each for their
education, training and support, or a toLal of ^800,000,000, But
after their lifetime, the tragedy of long life without sight because
'See appendix B for brief review of cozifirming statistics
- 11 -
of retrolental fibroplasia will have virtually ceased and so will
the heavy economic burden to the Nation.
At the same scientific meeting at which the results of the
retrolental fibroplasia study was presented, an Institute investi-
gator in the Bethesda program also presented a paper of intense
interest to the gathering of ophthalmologists from all over the
United States and Europe. To this audience came the first report
anywhere of a treatment for a form of granulomatous uveitis, an
incurable infection of the back of the eye, especially the retina,
vrhich is responsible for 5 to 7 percent of blindness in this country.
VJhile results were preliminary, they seemed promising. Of
29 cases admitted to the Clinical Center with granulomatous uveitis
caused by the parasite Toxoplasma, 2? cases had responded to a therapy
with two drugs - pyrimethamj.ne (Daraprim) and sulfanilamide. Of the
remaining four patients treated, three had not been treated long
enough for final evaluation.
The success of this therapy is still to be determined. Further
tests viill show whether the drugs are a cure or a controls it is
still possible that the infection vdll recur, requiring further
treatment, Daraprim, moreover, in the heavy dosages required in
the therapy of granulomatous uveitis, causes loss of appetite and
consequent loss of weight, /hile this side effect is reversed when
treatment is terminated, possibly some other drug will be found just
as effective but less toxic. ITiatever the final answer to these
- 12 -
problems are, they are somewhat academic to the patients who have
already received treatment at the Clinical Center. Their vision
has either been restored or improved, and those who had lost their
jobs because of failing vision have either regained them or found
This year also saw the advent of another drug added to the
armamentarium against ej'-e disease - Diamox, a specific for acute
glaucoma and a useful supplement for other drugs in the treatment
of other forms of the disorder. Glaucoma is a condition characterized
by increased pressure of the fluid in the eye which gradually shuts
off the blood supply to the retina. The results, unless pressure
can be relieved: permanent damage to the retina and permanent
blindness, as it now is for more than 55,000 persons in this country.
In last year's testimony, the research leading to the rational
use of Diamox against glaucoma was reviewed after the testimony proper
and inserted in the Record. It had been found that Diamox (a
sulfonamide derivative) could inhibit the activity of a certain
enzyme called carbonic anhydrase. Tliis enzyme is responsible for
the formation of sodium bicarbonate in the Intraocular fluid of the
3y eye, and sodium bicarbonate is associated" with that accumulation of
intraocular fluid in'^the eye characteristic of oriaucoma. It was
thus that last year Diamox was first tested for glaucoma and first
found to be of particular value in reducing the pressure- in acute
glaucoma, thereby permitting the intervention of surgerj'-.
- 13 -
It vras then thought that Diamox was relatively limited; it
seemed that lowering of the intraocular pressure could be achieved
for only a relatively short period of time. Studies by other grantees
this year, however, indicate this limitation does not exist, for with
refined methods of administration, Diamox has proved to be effective
in the long-term treatment of chronic glaucoma, the most common form
of the condition. Possibly the most significant factor in the find- ■
ing of Diamox lies in the fact that it is the first drug yet discovered,
to inhibit the formation of intraocular fluid, and it thereby sets
the pattern for an entirely nexj course in pharmacological investigation
which will almost certainly lead to the development of more successful
In good part, the problem of ^ilaucoma is one of early detection,
for found early and treated early, glaucoma should blind only infre-
quently. Partly responsible for the higher incidence of blindness
from this disease is the failure of the average individual to obtain
regular eye examinations; and almost equally important is the inability
of the average practitioner to diagnose the condition at its incipience.
Solution of this problem is now at hand with the development of
a simple instrument devised for the general practitioner--the Berens-
Tolman tonometer, itested gently on the eyeball (after the adminis-
tration of local anesthesia), it simply records x\rhether the intraocular
pressure is high or low — but not precisely how high or low, as do
more specialized instruments now in use. If the pressure is found
- lU -
higher than normal with the Berens-Tolman tonometer, eye examination
by an ophthalmologist is indicated to determine the exact nature of
At the present time, some 200 to 300 ophthalmologists in the
United States and burope are training general practitioners to use
this instrument and in so doing have alrear^,/ proved its enorm.ous
practicality. Some ij.0 percent of those patients already referred
to trained ophthalmologists because of abnormal register of the new
tonometer have proved to have incipient glaucoma.
These four advances mark'-the more dramatic developments in the
Institute's programs during the past year. Lany major problems still
concern us and it is to be expected tliat for such problems as cerebral
palsy, muscular dystrophy, multiple sclerosis, and cataract a series
of progressive steps lie ahead before the final aci-iievements in
prevention and treatment are obtained. That tliis year saw many such
steps taken iras perhaps as heartening and Important as the clear
clinical accomplishm.ents so far mentioned.
The House Subcommittee on iippropriations for the Department
of Health, Education, and Vjelfare has alread;/ received a complete
review of the extensive, nationwide attack on cerebral palsy being
spearheaded by the Institute, There are txro broad purposes in tlij-s
collaborative effort: 1) to establish a more precise determination of
fetal, environmental and medical factors leading to the various
forms of human cerebral palsy, and 2) to definitely link the various
- 1^ -
symptoms of this group of disorders to the causative brain damage,
in the first instance, we expect to create a sound rationale for care
of the pregnant mother and newborn child in order to prevent cerebral
palsy. In the second instance, our understanding of basic nervous
system control over motor (muscular) activity should lead to more
etiological clues, to a radical irprovement of methods of rehabilitation,
and to the development of new surgical techniques or new drugs for
improving the performance of the cerebral palsy patient.
Significant individual developments made during the last
year focus on studies of brain damage as it occurs during intrauterine
life. Because brain damage to the child most often occurs during the
cliild's embryonic growth, the creation and study of experimental cerebral
palsy in animals provides the bost Oj.-portunity for assessing the
causative factors leading to several clinical types of cerebral palsy.
As mentioned last year, experimental jv-ray irradiation of
pregnant rats has indicated that various cerebral palsy symptoms
which appear in newborn rats can be controlled. by varying the time
of irradiation during gestation. Institute experiments in creating
experimental cerebral palsy by anoxia (oxygen suffocation) confirm
the fact that the time of embryonic brain grovrth is central to the
kind and degree of brain damage achieved. The institute has also
been able to devise a technique for producing anoxia in selected
fetal animals without damaging the litter mates, thereby permitting
comparative evaluation of the cerebral palsied animal and his twin
"normal" after birth.
- 16 -
Brilliant studies by a ^^antee cast iurther light on tne
underlying, causation of cerebral palsy. Studies on the developing
brain of animals indicate that the significant energy producing
enz^Tne systems of the brain manifest different levels of activity
during gestation. These enz;Tne systems lie latent during certain
periods of brain development, but burst into critical activity at
specified times. Preliminary studies indicate that alteration in
the biocherrdstry of these enzymes at those speoifitd times is responr-
sible for certai. n symptoms of cerebral palsy. If such results
prove consistent, they will mark the first nope towards achievj.ng
reversal of the abnormal changes occuring during pregnancy probably
responsible for brain damage.
Other progress in cerebral oalsy : (a) bhe refinement of surgery
for the treatment of severe involuntary mo^ements. (b) the finding that
the immature liver's inability bo detoxify bile is partially respon-
sible for the development of kernicterus, thereby sugf^esting the
possibility for preventing the disorder as well as treating it,"'
(c) the development of a new research attack on nerve regeneration (because
nerve regeneration of mammals occurs in utero but not postnaLally, the
possible biochemical changes involved in this ciiange are being investi-
'"Last year's test-'mony presented the results on the development of a
treatment of this disease, previously responsible for causing 10 percent
of cerebral palsy in children.
- 17 -
The research attack on multiple sclerosis up until five years
ago had in good part been limited to experimental therapy and several
thousand drugs have hopefully been tested on this disorder. As it
must, this trial and eri'or approach continues, and the hopes of
multiple sclerotics were again raised by a report this year that the
antitubercular drug, isoniazid, had proved useful in the amelioration
of symptoms in several multiple sclerosis patients.
To obtain a decisive ansvxer which would either provide more
definite rationale for isoniazid therapy or whic:i would stem the
growing and possibly dangerous use of isoniazid by multiple sclerotics,
the Institute immediately initiated a pilot project for objective
evaluation of the drug. This project is not yet concluded, but
preliminary results should be available within the near future,
'iilhatever the results, establishment of this "double blind" clinical
trial has set it he technique for rapid evaluation of promising but
unproved results achieved at other laboratories where facilities do
not permit complete exploitation of their observations.
It seems clear that the most successful developments in the
attack on multiple sclerosis must come through an understanding of
the basic mechanisms involved in its causation. Several methods of
approach presently obtain as a result of recent findings and others
undoubtedly will develop. It has been found, for example, that
where myelin is destroyed during the course of multiple sclerosis
(this is the main pathological process of the disease), the small
- 18 -
sujportinj,, cellB oi' the nervous systein (nob nerve cells themselves)
tend to disappear. These supporting cells, which are called
oligodendroglia, are believed to play some role in the formation
and nutrition oi' myelin, and further studies at the Institute xdll
attempt to clarify this association.
The problem of myelin structure and activity is at the core
of the research attack on multiple sclerosis, and tnis research is
just now becoming productive, IMle it had previously been believed
that the myelin sheath was simply a protective covering for the nerve
fibres, we now iiave reason to believe ib plays sn active role in the
conduction of the nerve Impulse.
The nerve impulse passes along the nerve fibres in association
with the interaction of two cheroicals, sodium and potassium. As
transmission of the impulse occurs, potassium iri.tlxin the nerve cell
leaves the cell 3 sodium outside of the cell enters. l\ recent report
indicates that in certain nerve fibres not sixeathed ijith myelin,
potassium loss from the cell is some 2^ percent greater than in
those nerve cells i/hose fibres are myelinated. The unmyelinated
fibres, moreover, perform less activity, more slowly, than myelinated
fibres. In snort, this finding would strongly suggest that myelin
seems to have something to do vrith retention of potassium within
the cell and tiiereby with the speed and activity of the nerve impulse.
It should be mentioned here that the study of idultiple sclerosis
has been hampered by our inability to create the disease in animals.
- 19 -
A recent report indicates that a canine disease, apparently sindlar
to nultiple sclerosis in humans, occurs ^dtU some frequency ajiiong
Boxer dogs, and this exciting possibility will be explored further.
Last year, it was mentioned that progress had been obtained
in devising a diagnostic test for ruultiple sclerosis, which liitherto
has talcen an average of six years to identify medically. Abnormal
elevation of gamraa globulin in the spinal flui'-l of multiple sclerotics
is the basis of this diagnostic test, and tiiis year improvements have
been made at the Institute and by a grantee in the development of a
simple method for protein-spinal fluid concentration so that anaJ-ysis
of gamma globulin levels may be facilitated, frelimnary data also
indicates that ratio of gamraa globulin protein to spinal fluid may
relate to the progressive course of the disease and thereby provide
us with a method for establishing prognosis,
IflSCULii.t ^JYbXnO.^ilT AND riJlJ..Oi;USCUj^'u. DISOhDE^.S
In the last fiscal year an important se;i,meat of the institute's
program at the Clinic^al Center has focused a broad attaclc on neuro-
muscular disorders, which, by themselves alone, constitute a serious
public health problem. Some of these disorders, muscular dystrophy
and myasthenia gravis, can be rapid killersj while others, mj/ositis
and neuritis, can be chronic cripplers. Lieuromuscular disorders may
arise anywhere along the neuromuscular axis from the muscle to the
brain. Thus, in muscular dystrophy, the pripiary pathology is in the
muscle; in myasthenia gravis there is a failure in chemical trans-
mission at the ooint where the nerves become imbedded in the muscle.
- 20 -
(nerve -muscle junction) | and in infantile paralysis and other forms
of myelitis the damage takes place in the spinal cord.
Except for infantile paralysis, clinical research in neuro-
muscular disorders was relatively nonexistent before the activation
of this Institute in 1951. The causes of these conditions were
unknown and no fruitful clues to pursue them had been established,
IJhen the Institute's program at the Clinical Center was started in
1953, the task of solving the problem of muscular dystrophy aiid
neuromuscular disorders was as imponderable as piecing together a
picture puzzle in which most of the essential parts are missing.
This meant that the research slate developed thus far had to be i;iped
clean and the fundamentals of these conditions had to be attacked on
many fronts by adapting to the prcblem nevjer techniques which have
been developed in biophysics, biochemistry and pharmacology.
Therefore, the Institute investigators began their Bethesda
program in neuromuscular disorders by developing new methods for
studying human muscle biopsies and the chemical nature of neuro-
muscular transmission J by constructing aew devices for determining
neuromuscular electronics j by perfecting a method for evaluating
the ionic exchange of sodium and potassium through the use of un-
stable radioisotopes! and by the application of the principles of
flame photometry and chromotography to the problems of neuromuscular
- 21 -
During the last fiscal year these ne;..r instruments and methodolo-
gies uwere perfected and used on patients \ath muscular dystrophy,
myositis, myasthenia gravis, dystropldc myotonia, and farrdlial peilodic
paralysis. A group of neuromuscular disorders were tested rather than
the muscular d/strophy alone so tliat if they all iiad some common
denom.inator, it would not be missed.
With perfection of new instruments and new technics, last year,
came the discovery that the muscle cells in muscular dystrophy could
not retain a normal amount of potassiim and were overloaded vdth sodium*
vias tills the cause of muscular dystrophy, or was it the consequence
of some deeper process inherent to the disorder? a careful study using
ra-lioisotope tracers iias revealed that the potassium deficit is a con-
sequence, not a cause, so the scientific probe has continued, i-.ecently,
this team of institute investigators have discovered another abnormal
metabolic disturbance in muscular dystrophy; the e xcx-etion of abnormal
amounts of a pentose sugar by patients vdth this disorder, the
significance of x,rhich is presently being examined,
ifnile the Instituoe's clinical researcii tearn in neuromuscular
disorders have made this fruitful discovery, an Institute grantee
has demonstrated that if a diet deficient in caoline is fed to rats
for more than 70 days it produces the symptoms of muscular dystrophy,
thereby providing still another lead for clinical research in this
These and other advances are beginidng to supply some of the
impoi^tant missing parts in the puzijle of our knowledge about muscular
- 22 -
dystrophy and neuromuscular disorders. Tiie a;";.dition of a fevi rnore
parts should enable Institute investigators to fit the pieces together
for a rational explanation and ultimate preveiition or control of these
Previous attempts to elucidate the cause of cataractj a disorder
marked by partial or complete opacity of the lens of the eye and re-
sponsible for more than 20 percent of the blindness in the Urjited
States, have largely been restricted to chemical or physical analysis
of the lens after cataract has formed. This approach has not been
fruitful in determining the changes in lens composition occuring ■
with the formation and growth of cataract, and it is now to the
problem of cataract as a function of growth and aging of the lens
that several scientists, both here at Bethesda and at other labora-
tories, are addressing themselves.
It is possible to cause experimental cataract in animals by
administration of the compound alloxan, a simple method of obtaining
and examining the lens at all stages of cataract formation has been
ds'''ic3d by a grantee through sacrifice oi experimental animals with
cataract at various time intervals during cataract development. On
the basis of 108 lens obtained from Sk experimental rats, the
pathological sequence of events leading to lens opacity has been
established, and it is expected further studies will illuminate the
key biochemical alteraticns involved.
- 23 -
The method by iirhich alloxan causes cataract may also shed light
on its development, and tiiis approach has been initiated at the insti-
tute. That alloxan interferes ^^rith several ocular enzyme systems
is already known, and it has been confirmed that alloxan has an
affinity with the important sulfhydrl groups within the eye, U"hat
properties of all.oxan, however, are likely to influence these enzjniie
sj^'stems to cause cataract have yet to be clarified, and attempts,
therefore, to isolate these properties are now being made.
Experimental cataract may also be created through X-ray
irradiation, and another node of attack broached by the Institute
lies in the search for agents wliich can block this occurrence. An
amino acid called cystine has been found to have some inhibiting
effect on the formation of cataract when a applied to the eye prior
to irradiation, and exploration of this finding may illuminate the
chemistry of prevention and eventually suggest the clinical raeans
The review of research developments in the neuroloj^ical and
sensory disorders might be extended indefinitely. Some achievements
are not applicable to the larger categories of neui^ological and
sensory disease, though in some instances thej'' may well be as
important. These and other achievements are hereby listed, mth
further elaboration to be found in the institute's Highlights for
. 2U -
Discovery of a r!;Gtuod for measurement cf local cerebral blood
floi^ in animals viith potential application for hun^ans opens
up a new avenue for attack on the treatment and prevention
of cei'fcbral vascular disease (stroke) .
Further li^ht is being shed on the causes of peptic ulcer
in studies indicating the role of the hypothalamus and the
pituitary adrenal system in the secretion of gastric hydro-
Evidence has been produced that "intellectual deficits" may
be produced by lesions occurring in any portion of the
cerebral hemispheres 3 not chiefly by frontal lobe involvement
as previously believed.
The neurological mechanisms involved in the postural and move-
ment control of mammals have been elucidated^ thereby
illuminating further areas in the pathology of cerebral
It has I'Gcently been found that diabetic retinopathy, a
leading cause of blindness, is not directly related to the
severity of diabetss;^ it is a special disease of the eye and
kidney^ in which the metabolism of vitamin B-12 is affected.
A pupillograpliic machine has been developed which can measure
and record continuous minute changes in the eye's pupilj
thereby providing an invaluable tool for early diagnosis of
many eye and nervous disorders.
A surgical procedure has been devised for the relief of severe
cases of Parkinson's Disease (shaking palsy).
Calcific corneal opacities j such as result from certain burns
and diseases, can now be dissolved by means of a neutral
solution of the sodium salt of ethylene dianine tetraacetic
A new eye chart has been devised in which the type faces now
provide a maximum recognition factor and a minimum of confusion.
It has been found that the possibility of fatality in brain
surgery is frequently heralded by gastrointestinal hemorrhage
and ulceration, calling for replacement therapy, administration
of vitaiiiin K and, possibly, autonomic blocking agents.
BaL (253-dimercaptoproponal) Of Versene have been found
effective in the treatment of Wilson's Disease j a disorder
marked by progressive tremor, rigidity and mental deteriora-
Nasophar-.Tigeal irradiation has been found markedly effective
for the reduction of lymphoid tissue in the naso_jhar.'/n:c, the
major cause of hearing deficit in cnaldren.
KEoEAJtlCH AIID TKAlNlNG oUpPOivC
That increased support of research in the neurological and
sensory disorders nas resulted in significant gi'ant research achieve-
ment has already been ar.ply revealed, in jast years, such sup;jort
was relatively slight and the demand foi' research grants far e.cceeded
the institute's ability bo make them available.
In 19Sh, this situation was partially met by an increase of
appropriations, idiich jermitted the a^^f^.rd of 285 research grants in
the amount of •;?2,8l3j222. During this present year, with two of the
three Council meetings so far held for tlie approval of grants, ire.
have already been able to award 338 grants for ,)3 , l|.U2 , 206 . "' '/Jith
the continued increase of potential in neurological and sensory
disease research, it is clear that the next Council meeting -.dil lind
investigators with approved research projects more than r-ieeting the
total appropriation of >3, 900,000,
Testimony in oast years has indicated that one of the largest
gap areas has been the need for better iac3 lities in the graduate
■'''A :)pendix C - Grant Support hy Disease or Disoi'der
- 26 -
training of clinical teachers and researchers in neiirological and
sensory disorders. Up until 195h) less than one-tliird of all the
country's medical schools had complete neurological units for teach-
ing physicians and scientistsj many neurological teachers were not
qualified ne\irologistsj and, indeed, in several States in the United
States there was not a single qualified neurologist, teacher or other-
wise. In ophthalmology, while 150 specialists are being trained each
year, 300 are dying or retiring, and yet the general population
continues to swell steadily.
This situation is now being remedied. It began in 195Uj
where an initial budget of !i>l400,000 for training grants enabled us
to support 23 such programs. At this time this year, vjb have
already been able to support [|.0 of them at a cost of $712, UU?^ with
the total appropriation for the year of (1^900,000 already committed."*^
The same manifestation of the gathering importance of training
is revealed in every category of the training program. As of January 1,
1955 J 28 pre- and post-doctorate fellowships had been awarded, but
enough requests were already on hand to meet the total appropriation
of ^150,000, Again, 28 traineeships for $92,l4l40 have been awarded,
but 18 other qualified requests already exceed the appropriation of
$10[|.,000 for this purpose.
""'Appendix D - Training grant support ' by medical schools.
- 27 -
J'iEDICAL SCHOOLS aFD FRITTGIPAL li-WfiSTIlKTORS
PARTICIPATING IN EPIIiiPSI STUDIES VJITH ASFARAGINE
1) Children's Medical Center (Harvard Medical School)
Dr. Charles Davidson
2) University of North Carolina Medical School
Chapel Hill, North Carolina
Dr. Thomas Farmer
3) University of Virginia Medical School
Dr. Ualter K lineman
h) University of Buffalo Medical School
Biiff alo, New York
Dr. Bernard Sj.iith
5) University of Maryland Medical School
Dr. Charles Van Bus kirk
Appendix B - 2b
REVIEVJ OF PRELIICNARY STATISTICS EMERGING
FROM COLLABORATIVE STUDY OF RETROLENTAL FIBROPLASIA
1) Of 53 infants in 18 hospitals receiving routine oxyp;en
in their incubators, 72 percent incurred retrolental
fibroplasia, with 25 percent permanently blinded.
2) Of 2li5 infants, however, who had received curtailed
oxygen (for clinical crisis only), only 30 percent
developed the disease and less than 6 j^ercent suffered
loss of vision."" /
3) The mortality rate was 22.2 percent in routine oxygen
and 20sl percent for those in curtailed, indicating,
contrary to fears, that diminution of oxygen did not
increase the death rate.
*It is believed that even fewer cases will now occi'r because
of indications for greater caution due to the finding that
oxygen administration for even so short a period as three
days may cause retrolental fibroplasia.
RESEARCH GRANT SUPPORT BY CATEGORY OF DISEASE OR DISORDER
I. NEUROLOGIC DISORDERS
No , Amount
A. Cerebral Palsy and
B. Epilepsy & Other
C. Multiple Sclerosis
D. Muscular Dystrophy
E. General Metabolic &
of Nervous System
F. Poliomyelitis & Other
Infectious Diseases of
the Nervous System
G. Accident & Injury to
the Nervous System
H. Other Disorders of the
Nervous System not
111 - ^^k$3,986
59 - $535,006
31; - 536,285
27 - 231,621
U - 35/^Q9
3h - 2l;8,8U2
13 - 1W;,C05
Sub-total 189 2, 0U8, 505
^Includes funds already awarded or encumbered thus far in fiscal year 1955.
- 30 -
II. SENSORY DISORDERS Wo^ Amount No, Amount
A. Disorders of Hearing
and Balance 10 - ^ 9h,337 l6 - $17^,25?
Sub-total 10 9k, 337 16 17U,257
B. DisordfcxS of Vision
1. Cataract 7 - S3, 09$ 6 - l46,l471
2. Glaucoma 9 - 109, 26U 11 - 127,1^6
3. Retinopathy h - 38,898 9 - l)4l,503
U. Retrolental Fibroplasia l6 - 6l,ii90 10 - 83,06l
5, Uveitis J Keratitis,
& Other Inflammatory
& Parasitic Diseases 6 - 57,8^9 9 - 96,280
6. Metabolic & Degenera-
tive Diseases of the
Eye 22 - l6l,l8U 20 - 199,691;
7, Strabismus & Neuro-
muscular Disorders 2 - 3,381 2 - 9,C62
8. Other Ophthalmic
Injuries 5 - l|0,35l4 h - 32,^81
Sub-total 71 525,525 71 735,708
G. Disorders of the Other
Special Senses (taste,
smell, touch, & pain) l5 - liil,855 19 - 171;, OO8
Sub-total 15 1^1,855 19 17U,008
GRAND TOTAL 28U 2,810,222 338 3,14^2,206
'Includes funds already awarded or eiicmnbered thus far in fiscal year 1955.
C-RADmTE MEDICAL TR/iININQ GR/iNTS
ACTIVE AS OF FEBRUARY 1, 19'^S
University of California
District of Columbia
University of Chicago
State University of Iowa
University of Kansas
University of Louisville
The Johns Hopkins University
University of fferyland
University of MichiE^an " " $18,U68
University of Minnesota » " 17,8[|.3
Washington University " " lU,705
Albany Medical College « " 13', 111
University of Buffalo '"" "■ l6,k96
Columbia University " " 12,975
Columbia University " " 19,iil3
State University of New York " " 8,807
Montefiore Hospital ':" " 16,200
The Mount Sinai Hospital » " 15,120
New York University " " 15,279
University cxf North Carolina " " lit, 020
Bowman 'dray, School of Medicine " " 15,000
University of Oregon " » 16,992
University of Utah " » 21,020
University of Vermont it it lli,700
Tvilane University Ophthalmic disorders $18,^89
The Johns Hopkins University "
" 65, 19h
Harvard Medical School "
District of Coliwibia
Episcopal Eye, Ear
and Throat Hospital "
Washington University "
Cornell University "
University of North Carolina "
Ohio State University "
Western Reserve University "
University of Oregon "
Wills Eye Hospital "
Naiiontt rnstitutes ol Health
Bethesda 14, Maryland
4 0109 9699